William Christopher Wetsel

Journal Article Nat Commun · August 9, 2024 One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism ri ... Full text Link to item Cite

Presynaptic Rac1 in the hippocampus selectively regulates working memory.

Journal Article Elife · July 24, 2024 One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associat ... Full text Link to item Cite

Dopamine-Depleted Dopamine Transporter Knockout (DDD) Mice: Dyskinesia with L-DOPA and Dopamine D1 Agonists.

Journal Article Biomolecules · November 17, 2023 L-DOPA is the mainstay of treatment for Parkinson's disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia (LID) are dopamine-depleted dop ... Full text Link to item Cite

Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.

Journal Article Cell · May 11, 2023 The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has ... Full text Link to item Cite

Rescue of glutaric aciduria type I in mice by liver-directed therapies.

Journal Article Sci Transl Med · April 19, 2023 Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabol ... Full text Link to item Cite

Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice.

Journal Article Commun Biol · March 9, 2023 The underlying etiologies of seizures are highly heterogeneous and remain incompletely understood. While studying the unfolded protein response (UPR) pathways in the brain, we unexpectedly discovered that transgenic mice (XBP1s-TG) expressing spliced X-box ... Full text Link to item Cite

Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

Journal Article Br J Anaesth · February 2023 BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Her ... Full text Link to item Cite

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

Journal Article NMR Biomed · February 2023 The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on t ... Full text Link to item Cite

Identification and Characterization of ML321: A Novel and Highly Selective D2 Dopamine Receptor Antagonist with Efficacy in Animal Models That Predict Atypical Antipsychotic Activity.

Conference ACS Pharmacol Transl Sci · January 13, 2023 We have developed and characterized a novel D2R antagonist with exceptional GPCR selectivity - ML321. In functional profiling screens of 168 different GPCRs, ML321 showed little activity beyond potent inhibition of the D2R and to a lesser extent the D3R, d ... Full text Link to item Cite

The G protein biased serotonin 5-HT2A receptor agonist lisuride exerts anti-depressant drug-like activities in mice.

Journal Article Front Mol Biosci · 2023 There is now evidence from multiple Phase II clinical trials that psychedelic drugs can exert long-lasting anxiolytic, anti-depressant, and anti-drug abuse (nicotine and ethanol) effects in patients. Despite these benefits, the hallucinogenic actions of th ... Full text Link to item Cite

Establishment of multi-stage intravenous self-administration paradigms in mice.

Journal Article Sci Rep · December 11, 2022 Genetically tractable animal models provide needed strategies to resolve the biological basis of drug addiction. Intravenous self-administration (IVSA) is the gold standard for modeling psychostimulant and opioid addiction in animals, but technical limitat ... Full text Link to item Cite

Conserved YKL-40 changes in mice and humans after postoperative delirium.

Journal Article Brain Behav Immun Health · December 2022 Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to character ... Full text Link to item Cite

Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity.

Journal Article Nature · October 2022 There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally1-4. Efforts have focused on readily synthesizable molecules, inevitably leaving many chemotypes unexplored. Here we investi ... Full text Link to item Cite

Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment.

Journal Article Genes Brain Behav · September 2022 ProSAAS is a neuroendocrine protein that is cleaved by neuropeptide-processing enzymes into more than a dozen products including the bigLEN and PEN peptides, which bind and activate the receptors GPR171 and GPR83, respectively. Previous studies have sugges ... Full text Link to item Cite

Mice heterozygous for a null mutation of CPE show reduced expression of carboxypeptidase e mRNA and enzyme activity but normal physiology, behavior, and levels of neuropeptides.

Journal Article Brain Res · August 15, 2022 Carboxypeptidase E (CPE) is an essential enzyme that contributes to the biosynthesis of the vast majority of neuropeptides and peptide hormones. There are several reports claiming that small decreases in CPE activity cause physiological changes in animals ... Full text Link to item Cite

Characterization and Chemical Optimization of the D2 Dopamine Receptor-Selective Antagonist, ML321, Identifies Lead Compounds for the Clinical Treatment of Neuropsychiatric Disorders.

Journal Article FASEB J · May 2022 Schizophrenia is a devastating illness characterized by both positive (hallucinations, delusions) and negative (flat affect, decreased motivation) symptoms coupled with cognitive impairment. Current antipsychotic medications are effective in treating the p ... Full text Link to item Cite

Discovery of a functionally selective ghrelin receptor (GHSR1a) ligand for modulating brain dopamine.

Journal Article Proc Natl Acad Sci U S A · March 8, 2022 SignificanceThe modulation of growth hormone secretagogue receptor-1a (GHSR1a) signaling is a promising strategy for treating brain conditions of metabolism, aging, and addiction. GHSR1a activation results in pleiotropic physiological outcomes through dist ... Full text Link to item Cite

Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.

Journal Article Mol Psychiatry · March 2022 Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle reflex. PPI is a behavioral dimension deregulated in several neurological and psychiatric ... Full text Link to item Cite

Annexin-A1 Tripeptide Attenuates Surgery-Induced Neuroinflammation and Memory Deficits Through Regulation the NLRP3 Inflammasome.

Journal Article Front Immunol · 2022 Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically relevant orthopedic mouse model to study the impact of a common surgical proc ... Full text Link to item Cite

Ildr1 gene deletion protects against diet-induced obesity and hyperglycemia.

Journal Article PLoS One · 2022 OBJECTIVE: Immunoglobulin-like Domain-Containing Receptor 1 (ILDR1) is expressed on nutrient sensing cholecystokinin-positive enteroendocrine cells of the gastrointestinal tract and it has the unique ability to induce fat-mediated CCK secretion. However, t ... Full text Link to item Cite

LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1.

Journal Article Sci Rep · September 3, 2021 Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is ... Full text Link to item Cite

Psychedelic-inspired drug discovery using an engineered biosensor.

Journal Article Cell · May 13, 2021 Ligands can induce G protein-coupled receptors (GPCRs) to adopt a myriad of conformations, many of which play critical roles in determining the activation of specific signaling cascades associated with distinct functional and behavioral consequences. For e ... Full text Link to item Cite

Addition to "Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent In Vivo Antiparkinsonian Activity".

Journal Article ACS Chem Neurosci · April 21, 2021 Full text Link to item Cite

Neuropeptidomic Analysis of a Genetically Defined Cell Type in Mouse Brain and Pituitary.

Journal Article Cell Chem Biol · January 21, 2021 Neuropeptides and peptide hormones are important cell-cell signaling molecules that mediate many physiological processes. Unlike classic neurotransmitters, peptides undergo cell-type-specific post-translational modifications that affect their biological ac ... Full text Link to item Cite

Genetic deletion of Rgs12 in mice affects serotonin transporter expression and function in vivo and ex vivo.

Journal Article J Psychopharmacol · December 2020 BACKGROUND: Regulator of G protein Signaling (RGS) proteins inhibit G protein-coupled receptor (GPCR) signaling, including the signals that arise from neurotransmitter release. We have shown that RGS12 loss diminishes locomotor responses of C57BL/6J mice t ... Full text Link to item Cite

PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia.

Journal Article Nat Commun · November 19, 2020 The neuronal primary cilium and centriolar satellites have functions in neurogenesis, but little is known about their roles in the postnatal brain. We show that ablation of pericentriolar material 1 in the mouse leads to progressive ciliary, anatomical, ps ... Full text Link to item Cite

Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice.

Journal Article FASEB J · November 2020 Small ubiquitin-like modifier (SUMO1-3) conjugation (SUMOylation), a posttranslational modification, modulates almost all major cellular processes. Mounting evidence indicates that SUMOylation plays a crucial role in maintaining and regulating neural funct ... Full text Open Access Link to item Cite

β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.

Journal Article Cell · June 11, 2020 Small molecule neurotensin receptor 1 (NTSR1) agonists have been pursued for more than 40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical development of NTSR1 agonists has, however, been precluded by their seve ... Full text Link to item Cite

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia.

Journal Article Alzheimers Dement · May 2020 OBJECTIVE: The present work evaluates the relationship between postoperative immune and neurovascular changes and the pathogenesis of surgery-induced delirium superimposed on dementia. BACKGROUND AND RATIONALE: Postoperative delirium is a common complicati ... Full text Link to item Cite

The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders.

Journal Article J Neuroinflammation · October 28, 2019 BACKGROUND: Patients with pre-existing neurodegenerative disease commonly experience fractures that require orthopedic surgery. Perioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complicati ... Full text Link to item Cite

Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent In Vivo Antiparkinsonian Activity.

Journal Article ACS Chem Neurosci · September 18, 2019 Dopamine receptors are important G protein-coupled receptors (GPCRs) with therapeutic opportunities for treating Parkinson's Disease (PD) motor and cognitive deficits. Biased D1 dopamine ligands that differentially activate G protein over β-arrestin recrui ... Full text Link to item Cite

Erratum to ‘Electroconvulsive stimulation increases astrocyte marker GFAP in mouse hippocampus regardless of chronic social defeat stress’ (Brain Stimulation (2019) 12(2) (543), (S1935861X18312105), (10.1016/j.brs.2018.12.791))

Journal Article Brain Stimulation · September 1, 2019 The title of this abstract was incorrectly published as ‘Electroconvulsive stimulation increases astrocytes in mice subjected to chronic social defeat stress’. The correct title is above. The Publisher apologises for this error. ... Full text Cite

ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity.

Journal Article Proc Natl Acad Sci U S A · July 23, 2019 Giant ankyrin-B (ankB) is a neurospecific alternatively spliced variant of ANK2, a high-confidence autism spectrum disorder (ASD) gene. We report that a mouse model for human ASD mutation of giant ankB exhibits increased axonal branching in cultured neuron ... Full text Link to item Cite

Multivariate MR biomarkers better predict cognitive dysfunction in mouse models of Alzheimer's disease.

Journal Article Magn Reson Imaging · July 2019 To understand multifactorial conditions such as Alzheimer's disease (AD) we need brain signatures that predict the impact of multiple pathologies and their interactions. To help uncover the relationships between pathology affected brain circuits and cognit ... Full text Link to item Cite

Postsynaptic Mechanisms Render Syn I/II/III Mice Highly Responsive to Psychostimulants.

Journal Article Int J Neuropsychopharmacol · July 1, 2019 BACKGROUND: Synapsins are encoded by SYN I, SYN II, and SYN III, and they regulate neurotransmitter release by maintaining a reserve pool of synaptic vesicles. METHODS: Presynaptic dopamine responses to cocaine were examined by microdialysis, and postsynap ... Full text Link to item Cite

D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine.

Journal Article J Med Chem · May 9, 2019 Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both Gi/o-biased and β-a ... Full text Link to item Cite

Kctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions.

Journal Article Hum Mol Genet · May 1, 2019 The 16p11.2 BP4-BP5 deletion and duplication syndromes are associated with a complex spectrum of neurodevelopmental phenotypes that includes developmental delay and autism spectrum disorder, with a reciprocal effect on head circumference, brain structure a ... Full text Link to item Cite

Relative abundance of Akkermansia spp. and other bacterial phylotypes correlates with anxiety- and depressive-like behavior following social defeat in mice.

Journal Article Sci Rep · March 1, 2019 As discussion of stress and stress-related disorders rapidly extends beyond the brain, gut microbiota have emerged as a promising contributor to individual differences in the risk of illness, disease course, and treatment response. Here, we employed chroni ... Full text Link to item Cite

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice.

Journal Article Brain Stimul · 2019 BACKGROUND: The vagus nerve is involved in regulating immunity and resolving inflammation. Current strategies aimed at modulating neuroinflammation and cognitive decline, in many cases, are limited and ineffective. OBJECTIVE: We sought to develop a minimal ... Full text Link to item Cite

Correction: Comparative evaluation of a new magnetic bead-based DNA extraction method from fecal samples for downstream next-generation 16S rRNA gene sequencing.

Journal Article PLoS One · 2019 [This corrects the article DOI: 10.1371/journal.pone.0202858.]. ... Full text Link to item Cite

Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

Journal Article Front Immunol · 2019 Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limit ... Full text Link to item Cite

Novel E815K knock-in mouse model of alternating hemiplegia of childhood.

Journal Article Neurobiol Dis · November 2018 De novo mutations causing dysfunction of the ATP1A3 gene, which encodes the α3 subunit of Na+/K+-ATPase pump expressed in neurons, result in alternating hemiplegia of childhood (AHC). AHC manifests as paroxysmal episodes of hemiplegia, dystonia, behavioral ... Full text Link to item Cite

Brain region-specific disruption of Shank3 in mice reveals a dissociation for cortical and striatal circuits in autism-related behaviors.

Journal Article Transl Psychiatry · April 27, 2018 We previously reported a new line of Shank3 mutant mice which led to a complete loss of Shank3 by deleting exons 4-22 (Δe4-22) globally. Δe4-22 mice display robust ASD-like behaviors including impaired social interaction and communication, increased stereo ... Full text Link to item Cite

Parvalbumin Interneurons of the Mouse Nucleus Accumbens are Required For Amphetamine-Induced Locomotor Sensitization and Conditioned Place Preference.

Journal Article Neuropsychopharmacology · April 2018 To determine the requirement for parvalbumin (PV) expressing GABAergic interneurons of the nucleus accumbens (NAc) in the behavioral adaptations induced by amphetamine (AMPH), we blocked synaptic vesicle release from these neurons using Cre-inducible viral ... Full text Link to item Cite

GIT1 regulates synaptic structural plasticity underlying learning.

Journal Article PLoS One · 2018 The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor acti ... Full text Link to item Cite

Comparative evaluation of a new magnetic bead-based DNA extraction method from fecal samples for downstream next-generation 16S rRNA gene sequencing.

Journal Article PLoS One · 2018 We are colonized by a vast population of genetically diverse microbes, the majority of which are unculturable bacteria that reside within the gastrointestinal tract. As affordable, advanced next-generation sequencing technologies become more widely availab ... Full text Link to item Cite

Distinct neuronal populations in the basolateral and central amygdala are activated with acute pain, conditioned fear, and fear-conditioned analgesia.

Journal Article Neurosci Lett · November 20, 2017 Fear-conditioned analgesia (FCA) is modulated by brain areas involved in the descending inhibitory pain pathway such as the basolateral (BLA) and central amygdala (CEA). The BLA contains Ca2+/calmodulin-dependent protein kinase II (CaMKII) and parvalbumin ... Full text Link to item Cite

ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine.

Journal Article J Neurochem · November 2017 To identify neuropeptides that are regulated by cocaine, we used a quantitative peptidomic technique to examine the relative levels of neuropeptides in several regions of mouse brain following daily intraperitoneal administration of 10 mg/kg cocaine or sal ... Full text Link to item Cite

Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers.

Journal Article JCI Insight · October 19, 2017 Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underly ... Full text Link to item Cite

5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice.

Journal Article Neuropsychopharmacology · October 2017 All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side effects, and provide only partial amelioration of ... Full text Link to item Cite

Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration.

Journal Article Genes Brain Behav · June 2017 Parkinson's disease is a debilitating neurodegenerative condition for which there is no cure. Converging evidence implicates gangliosides in the pathogenesis of several neurodegenerative diseases, suggesting a potential new class of therapeutic targets. We ... Full text Link to item Cite

Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes.

Journal Article Dis Model Mech · May 1, 2017 The pathogenic drivers of sporadic and familial motor neuron disease (MND), such amyotrophic lateral sclerosis (ALS), are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-eff ... Full text Link to item Cite

G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in Caenorhabditis elegans.

Journal Article J Biol Chem · April 7, 2017 G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating ... Full text Link to item Cite

Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties.

Journal Article Proc Natl Acad Sci U S A · December 13, 2016 The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they ... Full text Link to item Cite

The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.

Journal Article Neuroimage · November 15, 2016 Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help ... Full text Link to item Cite

Increased Metabotropic Glutamate Receptor 5 Signaling Underlies Obsessive-Compulsive Disorder-like Behavioral and Striatal Circuit Abnormalities in Mice.

Journal Article Biol Psychiatry · October 1, 2016 BACKGROUND: Development of treatments for obsessive-compulsive disorder (OCD) is hampered by a lack of mechanistic understanding about this prevalent neuropsychiatric condition. Although circuit changes such as elevated frontostriatal activity are linked t ... Full text Link to item Cite

Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models.

Journal Article Neurobiol Dis · September 2016 Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. ... Full text Link to item Cite

ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse.

Journal Article ACS Chem Biol · July 15, 2016 Pharmacological treatment for methamphetamine addiction will provide important societal benefits. Neurotensin receptor NTR1 and dopamine receptor distributions coincide in brain areas regulating methamphetamine-associated reward, and neurotensin peptides p ... Full text Link to item Cite

Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress.

Journal Article J Neurosci Res · June 2016 Traumatic brain injury (TBI) is a leading cause of death and disability among young adults and is highly prevalent among recently deployed military personnel. Survivors of TBI often experience cognitive and emotional deficits, suggesting that long-term eff ... Full text Link to item Cite

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

Journal Article Environ Mol Mutagen · June 2016 Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have ... Full text Link to item Cite

Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.

Journal Article Nat Commun · May 10, 2016 Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout m ... Full text Open Access Link to item Cite

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons.

Journal Article Neuropsychopharmacology · April 2016 Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes-hours) and long period of time (days-weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the la ... Full text Link to item Cite

Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats.

Journal Article Invest New Drugs · April 2016 D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2 ... Full text Link to item Cite

Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice.

Journal Article Proc Natl Acad Sci U S A · March 29, 2016 Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeos ... Full text Link to item Cite

Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice.

Journal Article Neuropsychopharmacology · February 2016 Current antipsychotic drugs (APDs) show efficacy with positive symptoms, but are limited in treating negative or cognitive features of schizophrenia. Whereas all currently FDA-approved medications target primarily the dopamine D2 receptor (D2R) to inhibit ... Full text Link to item Cite

Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models.

Journal Article J Med Chem · January 28, 2016 A series of novel compounds with two halogen substituents have been designed and synthesized to further optimize the 2-phenylcyclopropylmethylamine scaffold in the quest for drug-like 5-HT2C agonists. Compound (+)-22a was identified as a potent 5-HT2C rece ... Full text Link to item Cite

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine.

Journal Article PLoS One · 2016 RATIONALE: The sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. N ... Full text Link to item Cite

Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

Journal Article PLoS One · 2016 Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD), a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model ... Full text Open Access Link to item Cite

Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury.

Journal Article Ann Rheum Dis · November 2015 OBJECTIVE: The mechanisms linking obesity and osteoarthritis (OA) are not fully understood and have been generally attributed to increased weight, rather than metabolic or inflammatory factors. Here, we examined the influence of fatty acids, adipokines, an ... Full text Link to item Cite

Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder.

Journal Article Sci Rep · September 23, 2015 Mutations that reduce expression or give rise to a Thr85Ser (T85S) mutation of Ca(2+)-CaM-dependent protein kinase kinase-2 (CaMKK2) have been implicated in behavioural disorders such as anxiety, bipolar and schizophrenia in humans. Here we report that Thr ... Full text Link to item Cite

Neurotrophic factor-α1 prevents stress-induced depression through enhancement of neurogenesis and is activated by rosiglitazone.

Journal Article Mol Psychiatry · June 2015 Major depressive disorder is often linked to stress. Although short-term stress is without effect in mice, prolonged stress leads to depressive-like behavior, indicating that an allostatic mechanism exists in this difference. Here we demonstrate that mice ... Full text Link to item Cite

Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.

Journal Article Nat Neurosci · June 2015 Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical beh ... Full text Link to item Cite

Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.

Journal Article Psychoneuroendocrinology · March 2015 Brain 5-HT deficiency has long been implicated in psychiatric disease, but the effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early life stress (ELS) has been suggested to contribute to adult psychopathology, but efforts to stu ... Full text Link to item Cite

Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents.

Journal Article J Med Chem · February 26, 2015 The discovery of a new series of compounds that are potent, selective 5-HT2C receptor agonists is described herein as we continue our efforts to optimize the 2-phenylcyclopropylmethylamine scaffold. Modifications focused on the alkoxyl substituent present ... Full text Link to item Cite

Radioprotection of the brain white matter by Mn(III) n-Butoxyethylpyridylporphyrin-based superoxide dismutase mimic MnTnBuOE-2-PyP5+.

Journal Article Mol Cancer Ther · January 2015 Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is though ... Full text Link to item Cite

Knock-in mouse model of alternating hemiplegia of childhood: behavioral and electrophysiologic characterization.

Journal Article Epilepsia · January 2015 OBJECTIVES: Mutations in the ATP1α3 subunit of the neuronal Na+/K+-ATPase are thought to be responsible for seizures, hemiplegias, and other symptoms of alternating hemiplegia of childhood (AHC). However, the mechanisms through which ATP1A3 mutations media ... Full text Link to item Cite

Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.

Journal Article J Psychiatry Neurosci · July 2014 BACKGROUND: Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experimen ... Full text Open Access Link to item Cite

In vivo and in vitro analyses of amygdalar function reveal a role for copper.

Journal Article J Neurophysiol · May 2014 Mice with a single copy of the peptide amidating monooxygenase (Pam) gene (PAM(+/-)) are impaired in contextual and cued fear conditioning. These abnormalities coincide with deficient long-term potentiation (LTP) at excitatory thalamic afferent synapses on ... Full text Link to item Cite

MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity.

Journal Article J Neurosci · March 26, 2014 The methyl-DNA binding protein MeCP2 is emerging as an important regulator of drug reinforcement processes. Psychostimulants induce phosphorylation of MeCP2 at Ser421; however, the functional significance of this posttranslational modification for addictiv ... Full text Link to item Cite

Peptidylglycine α-amidating monooxygenase heterozygosity alters brain copper handling with region specificity.

Journal Article J Neurochem · December 2013 Copper (Cu), an essential trace element present throughout the mammalian nervous system, is crucial for normal synaptic function. Neuronal handling of Cu is poorly understood. We studied the localization and expression of Atp7a, the major intracellular Cu ... Full text Link to item Cite

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice.

Journal Article Proc Natl Acad Sci U S A · October 22, 2013 PC7 belongs to the proprotein convertase family, whose members are implicated in the cleavage of secretory precursors. The in vivo function of PC7 is unknown. Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1 cells coexpress ... Full text Link to item Cite

Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.

Journal Article Neuron · October 16, 2013 We analyzed four families that presented with a similar condition characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. We show that recessive mutations in the ASNS gene are responsible f ... Full text Link to item Cite

The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

Journal Article Int J Neuropsychopharmacol · October 2013 Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the develo ... Full text Link to item Cite

GPR171 is a hypothalamic G protein-coupled receptor for BigLEN, a neuropeptide involved in feeding.

Journal Article Proc Natl Acad Sci U S A · October 1, 2013 Multiple peptide systems, including neuropeptide Y, leptin, ghrelin, and others, are involved with the control of food intake and body weight. The peptide LENSSPQAPARRLLPP (BigLEN) has been proposed to act through an unknown receptor to regulate body weigh ... Full text Link to item Cite

Mouse Behavioral Models for Autism Spectrum Disorders

Journal Article · August 27, 2013 Full text Cite

Emergence of anxiety-like behaviours in depressive-like Cpe(fat/fat) mice.

Journal Article Int J Neuropsychopharmacol · August 2013 Cpe(fat/fat) mice have a point mutation in carboxypeptidase E (Cpe), an exopeptidase that removes C-terminal basic amino acids from intermediates to produce bioactive peptides. The mutation renders the enzyme inactive and unstable. The absence of Cpe activ ... Full text Link to item Cite

Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy.

Journal Article Neuron · July 10, 2013 Temporal lobe epilepsy is the most common and often devastating form of human epilepsy. The molecular mechanism underlying the development of temporal lobe epilepsy remains largely unknown. Emerging evidence suggests that activation of the BDNF receptor Tr ... Full text Open Access Link to item Cite

Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities.

Journal Article J Neurosci · April 3, 2013 Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known ... Full text Link to item Cite

D2 Functionally Selective Ligands: Novel Therapeutics?

Journal Article · January 1, 2013 Full text Cite

Peptidylglycine α-amidating monooxygenase heterozygosity alters brain copper handling with region specificity

Journal Article Journal of Neurochemistry · 2013 Cite

Automated design of ligands to polypharmacological profiles.

Journal Article Nature · December 13, 2012 The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally ... Full text Link to item Cite

β-Arrestin-2 desensitizes the transient receptor potential vanilloid 1 (TRPV1) channel.

Journal Article J Biol Chem · October 26, 2012 Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated by multiple stimuli and is implicated in a variety of pain disorders. Dynamic sensitization of TRPV1 activity by A-kinase anchoring protein 150 demonstrates a criti ... Full text Link to item Cite

Structure-functional selectivity relationship studies of β-arrestin-biased dopamine D₂ receptor agonists.

Journal Article J Med Chem · August 23, 2012 Functionally selective G protein-coupled receptor (GPCR) ligands, which differentially modulate canonical and noncanonical signaling, are extremely useful for elucidating key signal transduction pathways essential for both the therapeutic actions and side ... Full text Link to item Cite

Pharmacologically-mediated reactivation and reconsolidation blockade of the psychostimulant-abuse circuit: a novel treatment strategy.

Journal Article Drug Alcohol Depend · July 1, 2012 Psychostimulant abuse continues to present legal, socioeconomic and medical challenges as a primary psychiatric disorder, and represents a significant comorbid factor in major psychiatric and medical illnesses. To date, monotherapeutic drug treatments have ... Full text Link to item Cite

New roles of carboxypeptidase E in endocrine and neural function and cancer.

Journal Article Endocr Rev · April 2012 Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protei ... Full text Link to item Cite

Mouse Behavioral Models for Autism Spectrum Disorders

Chapter · January 1, 2012 Full text Cite

Loss of deacetylation activity of Hdac6 affects emotional behavior in mice.

Journal Article PLoS One · 2012 Acetylation is mediated by acetyltransferases and deacetylases, and occurs not only on histones but also on diverse proteins. Although histone acetylation in chromatin structure and transcription has been well studied, the biological roles of non-histone a ... Full text Link to item Cite

Differential regulation of MeCP2 phosphorylation in the CNS by dopamine and serotonin.

Journal Article Neuropsychopharmacology · January 2012 Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain regions. Because AMPH simultaneously activates multiple monoamine neurotransmitter systems, he ... Full text Link to item Cite

Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.

Journal Article PLoS One · 2012 Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS), which has been suggested to enhance cognitive functions through GABA(A) receptor signaling by its metabolites. It has been shown that the level of pregnenolone ... Full text Link to item Cite

Mice deficient in endothelin-converting enzyme-2 exhibit abnormal responses to morphine and altered peptide levels in the spinal cord.

Journal Article J Neurochem · December 2011 An increasing body of evidence suggests that endothelin-converting enzyme-2 (ECE-2) is a non-classical neuropeptide processing enzyme. Similar to other neuropeptide processing enzymes, ECE-2 exhibits restricted neuroendocrine distribution, intracellular lo ... Full text Link to item Cite

Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy.

Journal Article Proc Natl Acad Sci U S A · November 8, 2011 Featured Publication Elucidating the key signal transduction pathways essential for both antipsychotic efficacy and side-effect profiles is essential for developing safer and more effective therapies. Recent work has highlighted noncanonical modes of dopamine D(2) receptor (D( ... Full text Link to item Cite

Opposite function of dopamine D1 and N-methyl-D-aspartate receptors in striatal cannabinoid-mediated signaling.

Journal Article Eur J Neurosci · November 2011 It is well established that the cannabinoid and dopamine systems interact at various levels to regulate basal ganglia function. Although it is well known that acute administration of cannabinoids to mice can modify dopamine-dependent behaviors, the intrane ... Full text Link to item Cite

Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.

Journal Article Neuron · October 6, 2011 Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neurona ... Full text Link to item Cite

Reversal of long-term methamphetamine sensitization by combination of pergolide with ondansetron or ketanserin, but not mirtazapine.

Journal Article Behav Brain Res · September 30, 2011 Psychostimulant abuse represents a psychiatric disorder and societal concern that has been largely unamenable to therapeutic interventions. We have previously demonstrated that the 5-HT₃ antagonist ondansetron or non-selective 5-HT(₂A/₂C) antagonist ketans ... Full text Link to item Cite

Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.

Journal Article Hum Mol Genet · August 1, 2011 Featured Publication SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Small microdeletions and point mutations in SHANK3 have been identified in a small subgroup of individuals with autism spectrum disorder (ASD) and i ... Full text Link to item Cite

Synapsin III: role in neuronal plasticity and disease.

Journal Article Semin Cell Dev Biol · June 2011 Synapsin III was discovered in 1998, more than two decades after the first two synapsins (synapsins I and II) were identified. Although the biology of synapsin III is not as well understood as synapsins I and II, this gene is emerging as an important facto ... Full text Link to item Cite

WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory.

Journal Article J Neurosci · February 16, 2011 The WAVE-associated Rac GAP, WRP, is thought to regulate key aspects of synapse development and function and may be linked to mental retardation in humans. WRP contains a newly described inverse F-BAR (IF-BAR) domain of unknown function. Our studies show t ... Full text Link to item Cite

Sensing hot and cold with TRP channels.

Journal Article Int J Hyperthermia · 2011 The past decade has witnessed the cloning of a new family of ion channels that are responsive to temperature. Six of these transient receptor potential (TRP) channels are proposed to be involved in thermosensation and are located in sensory nerves and skin ... Full text Link to item Cite

Neurophenotyping genetically modified mice for social behavior.

Journal Article Methods Mol Biol · 2011 Sociability in mice is a multidimensional adaptive and functional response. Due to its complexity, it is important that researchers use well-defined behavioral assays that are easily replicated with clearly defined ethograms. In the Mouse Behavioral and Ne ... Full text Link to item Cite

Hyperthermic effects on behavior.

Journal Article Int J Hyperthermia · 2011 This review focuses upon the past 8 years of research on hyperthermic effects on behavior. Heat stress and heat stoke become severe conditions when body temperatures exceed 40°C as this can lead to delirium, convulsions, coma, and death. The animal literat ... Full text Link to item Cite

Haploinsufficiency in peptidylglycine alpha-amidating monooxygenase leads to altered synaptic transmission in the amygdala and impaired emotional responses.

Journal Article J Neurosci · October 13, 2010 The mammalian amygdala expresses various neuropeptides whose signaling has been implicated in emotionality. Many neuropeptides require amidation for full activation by peptidylglycine α-amidating monooxygenase (PAM), a transmembrane vesicular cuproenzyme a ... Full text Link to item Cite

MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants.

Journal Article Nat Neurosci · September 2010 Featured Publication MeCP2 is a methyl DNA-binding transcriptional regulator that contributes to the development and function of CNS synapses; however, the requirement for MeCP2 in stimulus-regulated behavioral plasticity is not fully understood. Here we show that acute viral ... Full text Link to item Cite

Synapsins differentially control dopamine and serotonin release.

Journal Article J Neurosci · July 21, 2010 Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knock-out (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotra ... Full text Link to item Cite

Reduced cortical BDNF expression and aberrant memory in Carf knock-out mice.

Journal Article J Neurosci · June 2, 2010 Transcription factors are a key point of convergence between the cell-intrinsic and extracellular signals that guide synaptic development and brain plasticity. Calcium-response factor (CaRF) is a unique transcription factor first identified as a binding pr ... Full text Link to item Cite

TrkB signaling is required for behavioral sensitization and conditioned place preference induced by a single injection of cocaine.

Journal Article Neuropharmacology · June 2010 Exogenous brain-derived neurotrophic factor (BDNF) can regulate behavioral sensitization and conditioned place preference (CPP) when animals are exposed to repeated cocaine administration. However, it is unclear whether BDNF signaling through the TrkB rece ... Full text Link to item Cite

Mice lacking synapsin III show abnormalities in explicit memory and conditioned fear.

Journal Article Genes Brain Behav · April 2010 Synapsin III is a neuron-specific phosphoprotein that plays an important role in synaptic transmission and neural development. While synapsin III is abundant in embryonic brain, expression of the protein in adults is reduced and limited primarily to the hi ... Full text Link to item Cite

Integrin-linked kinase is involved in cocaine sensitization by regulating PSD-95 and synapsin I expression and GluR1 Ser845 phosphorylation.

Journal Article J Mol Neurosci · March 2010 Our recent studies have demonstrated that integrin-linked kinase (ILK) is involved in the induction and maintenance of cocaine behavioral sensitization and chronic cocaine-induced neural plasticity in the nucleus accumbens (NAc) core. In the present study, ... Full text Link to item Cite

Interactions of peptide amidation and copper: novel biomarkers and mechanisms of neural dysfunction.

Journal Article Neurobiol Dis · January 2010 Mammalian genomes encode only a small number of cuproenzymes. The many genes involved in coordinating copper uptake, distribution, storage and efflux make gene/nutrient interactions especially important for these cuproenzymes. Copper deficiency and copper ... Full text Link to item Cite

Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice.

Journal Article Arthritis Res Ther · 2010 INTRODUCTION: Obesity is a major risk factor for the development of osteoarthritis in both weight-bearing and nonweight-bearing joints. The mechanisms by which obesity influences the structural or symptomatic features of osteoarthritis are not well underst ... Full text Open Access Link to item Cite

Identification of 3-hydroxy-2-(3-hydroxyphenyl)-4H-1-benzopyran-4-ones as isoform-selective PKC-zeta inhibitors and potential therapeutics for psychostimulant abuse.

Journal Article Mol Biosyst · September 2009 From a screen of small molecule libraries to identify potential therapeutics for psychostimulant abuse, 3-hydroxy-2-(3-hydroxyphenyl)-4H-1-benzopyran-4-ones were shown to be isoform-selective PKC-zeta inhibitors. ... Full text Link to item Cite

Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.

Journal Article Arthritis Rheum · September 2009 OBJECTIVE: In mice with Col9a1 gene inactivation (Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1(-/-) mice for functional and symptomatic changes that may be assoc ... Full text Link to item Cite

Downregulation of NR3A-containing NMDARs is required for synapse maturation and memory consolidation.

Journal Article Neuron · August 13, 2009 NR3A is the only NMDA receptor (NMDAR) subunit that downregulates sharply prior to the onset of sensitive periods for plasticity, yet the functional importance of this transient expression remains unknown. To investigate whether removal/replacement of juve ... Full text Link to item Cite

Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor.

Journal Article Biochemistry · July 28, 2009 Salvinorin A, the most potent naturally occurring hallucinogen, has attracted an increasing amount of attention since the kappa-opioid receptor (KOR) was identified as its principal molecular target by us [Roth, B. L., et al. (2002) Proc. Natl. Acad. Sci. ... Full text Link to item Cite

An anxiety-like phenotype in mice selectively bred for aggression.

Journal Article Behav Brain Res · July 19, 2009 Using selective bi-directional breeding procedures, two different lines of mice were developed. The NC900 line is highly reactive and attacks their social partners without provocation, whereas aggression in NC100 animals is uncommon in social environments. ... Full text Link to item Cite

Impaired fear response in mice lacking GIT1.

Journal Article Neurosci Lett · July 17, 2009 G protein-coupled receptor kinase interacting protein 1 (GIT1) belongs to the family of Arf GAP proteins and has been implicated in the regulation of G protein-coupled receptor (GPCR) sequestration, cell migration, synapse formation and dendritic spine mor ... Full text Link to item Cite

Anxiety-like behaviors in mice lacking GIT2.

Journal Article Neurosci Lett · February 20, 2009 G protein-coupled receptor kinase-interactor 2 (GIT2) is a signaling scaffold protein that also functions as GTPase-activating protein (GAPs) for ADP-ribosylation factor (Arf) small GTP-binding proteins. GIT2 has been implicated in the regulation of G prot ... Full text Link to item Cite

Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking.

Journal Article J Neurochem · January 2009 Phosphorylation at glutamate receptor subunit 1(GluR1) Ser845 residue has been widely accepted to involve in GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking, but the in vivo evidence has not yet been es ... Full text Link to item Cite

Neural plasticity and addiction: integrin-linked kinase and cocaine behavioral sensitization.

Journal Article J Neurochem · November 2008 Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of biochemical molecules in different brain regions. However, which change is actually related to drug-produced sensitization lacks of accurate clarification. In this ... Full text Link to item Cite

Behavioral characterization of P311 knockout mice.

Journal Article Genes Brain Behav · October 2008 P311 is an 8-kDa protein that is expressed in many brain regions, particularly the hippocampus, cerebellum and olfactory lobes, and is under stringent regulation by developmental, mitogenic and other physiological stimuli. P311 is thought to be involved in ... Full text Link to item Cite

N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity.

Journal Article Neuropsychopharmacology · September 2008 Quetiapine is an atypical antipsychotic drug that is also US FDA approved for treating bipolar depression, albeit by an unknown mechanism. To discover the potential mechanism for this apparently unique action, we screened quetiapine, its metabolite N-Desal ... Full text Link to item Cite

High oxygen prevents fetal lethality due to lack of catecholamines.

Journal Article Am J Physiol Regul Integr Comp Physiol · September 2008 The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at embryonic day (E)13.5-14.5, they resemble wild-type (wt) fetuses expo ... Full text Link to item Cite

Adeno-associated virus-mediated ILK gene silencing in the rat NAc core.

Journal Article J Neurosci Methods · August 30, 2008 In this study we established conditional silencing of integrin-linked kinase (ILK) expression in Sprague-Dawley rat brain by microinjection of rAAV-2-carrying, Tet-On-regulated siRNA expression cassette into nucleus accumbens (NAc) core and induction with ... Full text Link to item Cite

Animals lacking endothelin-converting enzyme-2 are deficient in learning and memory.

Journal Article Genes Brain Behav · June 2008 Endothelin-converting enzyme (ECE)-2 is a metalloprotease that possesses many properties consistent with it being a neuropeptide-processing enzyme. This protease is found primarily in neural tissues, with high levels of expression in midbrain, cerebellum, ... Full text Link to item Cite

Reply to Belmaker et al.: GSK3β haploinsufficiency results in lithium-like effects in the forced-swim test

Journal Article Proceedings of the National Academy of Sciences of the United States of America · May 20, 2008 Full text Cite

Role of GSK3 beta in behavioral abnormalities induced by serotonin deficiency.

Journal Article Proc Natl Acad Sci U S A · January 29, 2008 Dysregulation of brain serotonin (5-HT) neurotransmission is thought to underlie mental conditions as diverse as depression, anxiety disorders, bipolar disorder, autism, and schizophrenia. Despite treatment of these conditions with serotonergic drugs, the ... Full text Link to item Cite

A beta-arrestin 2 signaling complex mediates lithium action on behavior.

Journal Article Cell · January 11, 2008 Besides their role in desensitization, beta-arrestin 1 and 2 promote the formation of signaling complexes allowing G protein-coupled receptors (GPCR) to signal independently from G proteins. Here we show that lithium, a pharmacological agent used for the m ... Full text Link to item Cite

Absence of carboxypeptidase E leads to adult hippocampal neuronal degeneration and memory deficits.

Journal Article Hippocampus · 2008 Molecules that govern the formation, integrity, and function of the hippocampus remain an important area of investigation. Here we show that absence of the proneuropeptide processing enzyme, carboxypeptidase E (CPE) in CPE knock-out (KO) mice had a profoun ... Full text Link to item Cite

Vmat2 heterozygous mutant mice display a depressive-like phenotype.

Journal Article J Neurosci · September 26, 2007 Featured Publication The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in ... Full text Link to item Cite

Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice.

Journal Article Nature · August 23, 2007 Featured Publication Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder characterized by persistent intrusive thoughts (obsessions) and repetitive actions (compulsions). Dysfunction of cortico-striato-thalamo-cortical circuitry is implicated in OCD, although t ... Full text Link to item Cite

Reduction of synapsin III in the prefrontal cortex of individuals with schizophrenia.

Journal Article Schizophr Res · August 2007 We analyzed the expression of a presynaptic protein, synapsin III, in individuals with schizophrenia. Since levels of synapsin III were previously found to be significantly reduced in the hippocampus of individuals with schizophrenia, we examined another b ... Full text Link to item Cite

Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity.

Journal Article Biochem Biophys Res Commun · May 11, 2007 We have recently shown in rats that cocaine-induced behavioral sensitization can be reversed by a 5-day treatment with ondansetron given 3.5 h after daily pergolide injections. In this study we further investigated the molecular/neurochemical alterations u ... Full text Link to item Cite

Neuroanatomical phenotypes in the reeler mouse.

Journal Article Neuroimage · February 15, 2007 The reeler mouse (Reln) has been proposed as a neurodevelopmental model for certain neurological and psychiatric conditions and has been studied by qualitative histochemistry and electron microscopy. Using magnetic resonance microscopy (MRM), we have quant ... Full text Link to item Cite

Reversal of cocaine-induced behavioral sensitization and associated phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors.

Journal Article Neuropsychopharmacology · February 2007 Cocaine abusers remain vulnerable to drug craving and relapse for many years after abstinence is achieved. We have recently shown that ondansetron (a 5-HT3 receptor antagonist) given 3.5 h after each daily cocaine injection reverses previously established ... Full text Link to item Cite

Methamphetamine induces long-term changes in GABAA receptor alpha2 subunit and GAD67 expression.

Journal Article Biochem Biophys Res Commun · December 8, 2006 The present study investigated whether GABA(A) receptor alpha2 subunit and GAD(67) are involved in chronic high dose methamphetamine (METH)-induced sensitization and neurotoxicity. The METH sensitization was established in rats by 7-day pump infusion plus ... Full text Link to item Cite

Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition.

Journal Article Neuron · September 7, 2006 An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetic ... Full text Link to item Cite

Cocaine increases dopamine release by mobilization of a synapsin-dependent reserve pool.

Journal Article J Neurosci · March 22, 2006 Cocaine primarily exerts its behavioral effects by enhancing dopaminergic neurotransmission, amplifying dopamine-encoded sensorimotor integration. The presumed mechanism for this effect is inhibition of the dopamine transporter, which blocks dopamine uptak ... Full text Link to item Cite

PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity.

Journal Article Biochem Biophys Res Commun · February 24, 2006 Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved in cell differentiation, proliferation, survival, and phagocytosis, and may participate in various brain functions. To determine whether it is also involved in cocaine sensiti ... Full text Link to item Cite

Assessments of cognitive deficits in mutant mice

Chapter · January 1, 2006 Although most behavioral experiments have been conducted in rats, mice are rapidly becoming the preferred rodent of study in many labs because their genetics are well known, their genome has been sequenced, and they can be genetically manipulated. To date, ... Cite

Novelty seeking and stereotypic activation of behavior in mice with disruption of the Dat1 gene.

Journal Article Neuropsychopharmacology · October 2005 Disruption of the dopamine (DA) transporter (Dat1) gene in mice leads to a 50% reduction or complete elimination of Dat1 expression in striatum of respective heterozygous (HZ) and knockout (KO) mice. Compared to wild-type (WT) controls, extracellular DA is ... Full text Link to item Cite

Regulation of gonadotropin-releasing hormone secretion by cannabinoids.

Journal Article Endocrinology · October 2005 Cannabinoids (CBs) exert untoward effects on reproduction by reducing LH secretion and suppressing gonadal function. Recent evidence suggests these effects are due primarily to hypothalamic dysfunction; however, the mechanism is obscure. Using immortalized ... Full text Link to item Cite

Erratum: Novelty seeking and stereotypic activation of behavior in mice with disruption of the DatI gene (Neuropsychopharmacology (April 27, 2005), DOI:10.1038/sj.npp.1300724)

Journal Article Neuropsychopharmacology · September 1, 2005 Full text Cite

Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease.

Journal Article PLoS Biol · August 2005 Featured Publication Brain dopamine is critically involved in movement control, and its deficiency is the primary cause of motor symptoms in Parkinson disease. Here we report development of an animal model of acute severe dopamine deficiency by using mice lacking the dopamine ... Full text Link to item Cite

Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior.

Journal Article J Neurosci · May 4, 2005 The extracellular region of the transmembrane neural cell adhesion molecule (NCAM-EC) is shed as a soluble fragment at elevated levels in the schizophrenic brain. A novel transgenic mouse line was generated to identify consequences on cortical development ... Full text Link to item Cite

Monoaminergic dysregulation in glutathione-deficient mice: possible relevance to schizophrenia?

Journal Article Neuroscience · 2005 Several lines of research have implicated glutathione (GSH) in schizophrenia. For instance, GSH deficiency has been reported in the prefrontal cortex of schizophrenics in vivo. Further, in rats postnatal GSH-deficiency combined with hyperdopaminergia led t ... Full text Link to item Cite

Different presynaptic roles of synapsins at excitatory and inhibitory synapses.

Journal Article J Neurosci · December 15, 2004 The functions of synapsins were examined by characterizing the phenotype of mice in which all three synapsin genes were knocked out. Although these triple knock-out mice were viable and had normal brain anatomy, they exhibited a number of behavioral defect ... Full text Link to item Cite

The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits.

Journal Article Endocrinology · December 2004 A carboxypeptidase E (CPE) knockout (KO) mouse was generated by deletion of exons 4 and 5 from the CPE gene, and its phenotype was characterized. KO mice became obese by 10-12 wk of age and reached 60-80 g by 40 wk. At this age, body fat content was more t ... Full text Link to item Cite

ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory.

Journal Article Mol Cell Biol · December 2004 The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dyn ... Full text Link to item Cite

Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2.

Journal Article Mol Cell Biol · May 2004 A family of orphan transporters has been discovered that are structurally related to the Na(+)-Cl(-)-dependent neurotransmitter transporters, including the dopamine transporter. One member of this family, the mouse XT2 gene, is predominantly expressed in t ... Full text Link to item Cite

Deficits in reproduction and pro-gonadotropin-releasing hormone processing in male Cpefat mice.

Journal Article Endocrinology · April 2004 Featured Publication Cpe(fat/fat) mice are obese, diabetic, and infertile. These animals have a point mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal basic amino acids from peptide intermediates. The mutation renders the enzyme unstable, and it is ... Full text Link to item Cite

Aberrant responses in social interaction of dopamine transporter knockout mice.

Journal Article Behav Brain Res · January 5, 2004 The dopamine (DA) transporter (DAT) controls the temporal and spatial resolution of dopaminergic neurotransmission. Disruption of the Dat1 gene in mice leads to increased extracellular DA concentrations and reduced expression of D1- and D2-like receptors i ... Full text Link to item Cite

Interaction of estrogen receptor alpha with protein kinase C alpha and c-Src in osteoblasts during differentiation.

Journal Article Bone · January 2004 In cultured osteoblasts, protein kinase C (PKC) activity increases and estrogen receptor alpha (ERalpha) binding capacity decreases upon confluence. We investigated potential interactions between ERalpha and PKC isoforms and their confluence-induced modula ... Full text Link to item Cite

Differential psychostimulant-induced activation of neural circuits in dopamine transporter knockout and wild type mice.

Journal Article Neuroscience · 2003 Dopamine (DA) is a neurotransmitter that has been implicated in a wide variety of psychiatric disorders that include attention deficit-hyperactivity disorder (ADHD), schizophrenia, and drug abuse. Recently, we have been working with a mouse in which the ge ... Full text Link to item Cite

Deficiencies in pro-thyrotropin-releasing hormone processing and abnormalities in thermoregulation in Cpefat/fat mice.

Journal Article J Biol Chem · December 13, 2002 Cpe(fat/fat) mice are obese, diabetic, and infertile. They have a mutation in carboxypeptidase E (CPE), an enzyme that converts prohormone intermediates to bioactive peptides. The Cpe(fat) mutation leads to rapid degradation of the enzyme. To test whether ... Full text Link to item Cite

Behavioral responses to social stress in noradrenaline transporter knockout mice: effects on social behavior and depression.

Journal Article Brain Res Bull · July 2002 Noradrenaline has been implicated in the pathogenesis of depression and the noradrenaline transporter (NET) is a target for some antidepressants. Therefore, mice with disrupted NET gene expression (NET-KO) appear especially suitable for studying this behav ... Full text Link to item Cite

Pro-GnRH processing.

Journal Article Prog Brain Res · 2002 Full text Link to item Cite

alpha(1)-adrenergic receptors mediate LH-releasing hormone secretion through phospholipases C and A(2) in immortalized hypothalamic neurons.

Journal Article Endocrinology · November 2001 Norepinephrine has long been known to stimulate the pulsatile and preovulatory release of LH-releasing hormone (LHRH). In vivo and in vitro studies indicate that these effects are mediated primarily through alpha(1)-adrenergic receptors (alpha(1)-ARs). Wit ... Full text Link to item Cite

Cerebellar defects in Ca2+/calmodulin kinase IV-deficient mice.

Journal Article J Neurosci · November 15, 2000 The Ca(2+)/calmodulin-dependent protein kinase CaMKIV was first identified in the cerebellum and has been implicated in nuclear signaling events that control neuronal growth, differentiation, and plasticity. To understand the physiological importance of Ca ... Full text Link to item Cite

The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures.

Journal Article Brain Res Mol Brain Res · June 23, 2000 The expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) after exposure to endotoxins has been implicated in immune-mediated neurotoxicity. The indolocarbazole compound Gö6976, which has been described as a selective ... Full text Link to item Cite

Post-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Gö6976 in murine microglia.

Journal Article Brain Res Mol Brain Res · June 23, 2000 Glia in the brain respond to various toxins with an increased expression of inducible nitric oxide synthase (iNOS) and an increased production of nitric oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of iNOS was down-regulated ... Full text Link to item Cite

Mice lacking the norepinephrine transporter are supersensitive to psychostimulants.

Journal Article Nat Neurosci · May 2000 The action of norepinephrine (NE) is terminated, in part, by its uptake into presynaptic noradrenergic neurons by the plasma-membrane NE transporter (NET), which is a target for antidepressants and psychostimulants. Disruption of the NET gene in mice prolo ... Full text Link to item Cite

"Model" behavior.

Journal Article Science · March 24, 2000 Full text Link to item Cite

Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.

Journal Article Eur J Biochem · June 1999 Endoproteolytic cleavage of protein prohormones often generates intermediates extended at the C-terminus by Arg-Arg or Lys-Arg, the removal of which by a carboxypeptidase (CPE) is normally an important step in the maturation of many peptide hormones. Recen ... Full text Link to item Cite

Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1beta.

Journal Article Endocrinology · June 1999 Mice carrying a null mutation for either of the two cyclooxygenase (COX) isoenzymes, necessary for prostanoid production, exhibit several isotype-specific reproductive abnormalities. Mice deficient in COX-1 are fertile but have decreased pup viability, whe ... Full text Link to item Cite

Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.

Journal Article Science · January 15, 1999 Featured Publication The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have e ... Full text Link to item Cite

Modulation of estrogen receptor levels in mouse uterus by protein kinase C isoenzymes.

Journal Article Endocrinology · November 1998 We have recently shown that protein kinase C (PKC) modifies estrogen receptor (ER) binding and modulates the responsiveness to estrogens in a clonal osteoblast-like cell line stably transfected with the ER. The purpose of the present study was to determine ... Full text Link to item Cite

Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice.

Journal Article Endocrinology · October 1998 Testicular androgens are integral components of the hormonal feedback loops that regulate circulating levels of LHbeta and FSH. The sites of feedback include hypothalamic areas regulating GnRH neurons and pituitary gonadotropes. To better define the roles ... Full text Link to item Cite

Protein kinase C modulates estrogen receptors in differentiated osteoblastic cells in vitro.

Journal Article Steroids · 1998 Several reports have shown an interaction between the estrogen receptor (ER) and the protein kinase C (PKC) intracellular pathways. Data from our laboratory showed that PKC activation can modulate ER levels and responsiveness in estrogen target tissues suc ... Full text Link to item Cite

Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats.

Journal Article Proc Natl Acad Sci U S A · December 9, 1997 Relationships were examined between spatial learning and hippocampal concentrations of the alpha, beta2, and gamma isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined f ... Full text Link to item Cite

Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia.

Journal Article Proc Natl Acad Sci U S A · October 14, 1997 An essential component of regulated steroidogenesis is the translocation of cholesterol from the cytoplasm to the inner mitochondrial membrane where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroidogenesis. Recent ... Full text Link to item Cite

Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter.

Journal Article Neuron · July 1997 Deletion of the dopamine transporter (DAT) results in increased dopaminergic tone, anterior pituitary hypoplasia, dwarfism, and an inability to lactate. DAT elimination alters the spatial distribution and dramatically reduces the numbers of lactotrophs and ... Full text Link to item Cite

Hypothalamic astrocytes respond to transforming growth factor-alpha with the secretion of neuroactive substances that stimulate the release of luteinizing hormone-releasing hormone.

Journal Article Endocrinology · January 1997 Previous studies demonstrated the involvement of transforming growth factor-alpha (TGF alpha), a member of the epidermal growth factor (EGF) family, in the developmental regulation of hypothalamic LHRH release. Although both TGF alpha and EGF stimulate LHR ... Full text Link to item Cite

Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex.

Journal Article J Neurochem · December 1996 Several laboratories have reported a lack of protein kinase C (PKC) activation in response to various stimuli in the brain of aged rats. It has been suggested that changes in lipid membrane composition could be related to this functional deficit. However, ... Full text Link to item Cite

The inhibition of differentiation caused by TGFbeta in fetal myoblasts is dependent upon selective expression of PKCtheta: a possible molecular basis for myoblast diversification during limb histogenesis.

Journal Article Dev Biol · November 25, 1996 Embryonic and fetal skeletal myoblasts are responsible for the formation of primary and secondary fibers in mammals, but the mechanism which diversifies their fate is unknown. In vitro, embryonic myoblasts are resistant to the differentiation inhibitory ef ... Full text Link to item Cite

Differential isoform-specific regulation of calcium-independent protein kinase C in rat cerebral cortex.

Journal Article Neurosci Lett · August 23, 1996 Regulation of the Ca(2+)-independent protein kinase C (PKC) activity and isoforms by phorbol esters was investigated in rat cerebral cortex. Loss of soluble PKC eta immunoreactivity from the soluble fraction was dramatic with only a small increase in the m ... Full text Link to item Cite

Neural and glial-mediated effects of growth factors acting via tyrosine kinase receptors on luteinizing hormone-releasing hormone neurons.

Journal Article Endocrinology · June 1996 It is becoming increasingly evident that the secretory activity of LHRH neurons is regulated not only by transsynaptic inputs but also by trophic molecules of glial and neuronal origin. The present experiments were undertaken to gain insights into the pote ... Full text Link to item Cite

Basic fibroblast growth factor regulates the conversion of pro-luteinizing hormone-releasing hormone (Pro-LHRH) to LHRH in immortalized hypothalamic neurons.

Journal Article Endocrinology · June 1996 Growth factors are commonly associated with the regulation of cellular proliferation and differentiation. In established cells, growth factors can also serve as trophic agents. Immortalized LHRH neurons contain basic fibroblast growth factor (bFGF) recepto ... Full text Link to item Cite

Effect of ischemic preconditioning and PKC activation on acidification during ischemia in rat heart.

Journal Article J Mol Cell Cardiol · May 1996 Ischemic preconditioning (PC) has been shown to attenuate intracellular acidification during a subsequent period of ischemia, to minimize stunning, and to decrease infarct size, PKC activation has been suggested to be involved in this phenomenon. The prese ... Full text Link to item Cite

NMDA and nitric oxide act through the cGMP signal transduction pathway to repress hypothalamic gonadotropin-releasing hormone gene expression.

Journal Article EMBO J · February 1, 1996 The key roles of the excitatory neurotransmitter glutamate and its second messengers, nitric oxide (NO) and cGMP, in long-term potentiation and neural plasticity are well documented. However, complex functions such as memory are likely to require long term ... Link to item Cite

Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts.

Journal Article Neurosci Lett · December 1, 1995 The present study shows that cultured fibroblasts from sporadic Alzheimer's disease patients are deficient in protein kinase C-regulated secretion of amyloid precursor protein. In particular, Alzheimer fibroblasts show a reduced basal secretion and a reduc ... Full text Link to item Cite

Expression of candidate pro-GnRH processing enzymes in rat hypothalamus and an immortalized hypothalamic neuronal cell line.

Journal Article Neuroendocrinology · August 1995 Since gonadotropin-releasing hormone (GnRH, also referred to as LHRH) is a major hormone regulating mammalian reproduction, identification of the processing steps involved in the conversion of the pro-LHRH to LHRH is fundamental to our understanding of its ... Full text Link to item Cite

Effects of insulin-like growth factors I and II and insulin on the immortalized hypothalamic GTI-7 cell line.

Journal Article Neuroendocrinology · August 1995 Insulin and insulin-like growth factor I (IGF-I) participate in energy metabolism, regulate cellular growth and differentiation, and are thought to act locally in a paracrine manner through specific receptors. Systemic levels of these peptides in humans an ... Full text Link to item Cite

Rapid activation and down-regulation of protein kinase C alpha in 12-O-Tetradecanoylphorbol-13-acetate-induced differentiation of human rhabdomyosarcoma cells.

Journal Article Cell Growth Differ · July 1995 Human rhabdomyosarcoma RD cells express the myogenic regulatory factors MyoD and myogenin but differentiate spontaneously very poorly. Prolonged treatment of RD cells with the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA) indu ... Link to item Cite

Immortalized hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons: a new tool for dissecting the molecular and cellular basis of LHRH physiology.

Journal Article Cell Mol Neurobiol · February 1995 1. Two LHRH neuronal cell lines were developed by targeted tumorigenesis of LHRH neurons in vivo. These cell lines (GN and GT-1 cells) represent a homogeneous population of neurons. GT-1 cells have been further subcloned to produce the GT1-1, GT1-3, and GT ... Full text Link to item Cite

Protein kinase C activity, translocation, and conventional isoforms in aging rat brain.

Journal Article Neurobiol Aging · 1995 Protein kinase C was studied in various brain areas in aging Wistar rats. Histone-directed kinase activity from the cortex, hippocampus and cerebellum did not change with aging. Using purified protein B-50 as a substrate, between 3 and 8 months a decrease ... Full text Link to item Cite

Characterization and distribution of protein kinase C isoforms in human skin fibroblasts.

Journal Article Arch Biochem Biophys · October 1994 In the present study we have examined the distribution of several isoforms of protein kinase C, a lipid-regulated serine/threonine kinase essential for signal transduction and cell regulation, in cultured human skin fibroblasts. By Western blot analysis we ... Full text Link to item Cite

Expression and regulation of calcium-independent protein kinase C in NG 108-15 cell differentiation.

Journal Article Biochem Biophys Res Commun · September 30, 1994 Protein, mRNA and activity levels of the calcium-independent protein kinase C (nPKC) isoenzymes were examined in NG108-15 cells. Western blot analyses reveal that proliferating NG 108-15 cells express the delta, epsilon, and eta, but not the theta species. ... Full text Link to item Cite

Regulation of protein kinase C in NG108-15 cell differentiation.

Journal Article Biochem Biophys Res Commun · May 30, 1994 The involvement of PKC in NG108-15 cell differentiation was investigated. Differentiation with dBcAMP was associated with a decrease in total cellular phorbol ester binding. The histone-directed PKC activity was decreased in the soluble fraction. Northern ... Full text Link to item Cite

Immunolocalization of PKC zeta in rat photoreceptor inner segments.

Journal Article Curr Eye Res · February 1994 We have utilized several peptide specific antisera directed against the C-terminals (Wetsel et al, 1992) of several protein kinase C (PKC) isozymes (alpha, beta 1, beta 11, gamma, delta, epsilon, zeta) to delineate the cellular localization of these PKC is ... Full text Link to item Cite

Differential expression of gamma-aminobutyric acid receptors in immortalized luteinizing hormone-releasing hormone neurons.

Journal Article Endocrinology · November 1993 gamma-Aminobutyric acid (GABA) has been shown both to stimulate and inhibit LH secretion in vivo. GABA apparently exerts these effects at the hypothalamic level by regulating the release of LHRH. In this study, we have investigated the effect of GABAergic ... Full text Link to item Cite

Light and electron microscopic immunocytochemical localization of PKC delta immunoreactivity in the rat central nervous system.

Journal Article J Comp Neurol · October 15, 1993 Protein kinase C (PKC) is one of the major cellular signal transduction systems. Since at least nine different PKC isoenzymes have been described, the purpose of the present studies was to identify the regional, cellular, and subcellular distributions of P ... Full text Link to item Cite

Endogenous protein kinase-C activation in osteoblast-like cells modulates responsiveness to estrogen and estrogen receptor levels.

Journal Article Mol Endocrinol · September 1993 The osteoblast-like osteosarcoma cell line ROS 17/2.8, which expresses very low levels of estrogen receptor (ER), was stably transfected with the mouse ER in order to more easily evaluate the physiological role of estrogens in bone cell homeostasis. These ... Full text Link to item Cite

Regulation of gonadotropin-releasing hormone by protein kinase-A and -C in immortalized hypothalamic neurons.

Journal Article Endocrinology · June 1993 As major signal transduction cascades, the protein kinase-A and -C (PKA and PKC) pathways have been implicated in the regulation of GnRH synthesis and secretion in the hypothalamus. We have investigated the roles of these pathways in the regulation of GnRH ... Full text Link to item Cite

Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets.

Journal Article J Biol Chem · March 5, 1993 Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to ... Link to item Cite

Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKC alpha.

Journal Article J Biol Chem · January 5, 1993 The multidrug resistance (MDR) phenotype induces cross-resistance to many chemotherapeutic agents in cancer cells. Protein kinase C (PKC) has been implicated in the regulation of the MDR phenotype. In order to determine the role of specific PKC isoenzymes ... Link to item Cite

Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone-secreting neurons.

Journal Article Proc Natl Acad Sci U S A · May 1, 1992 Mammalian reproduction is dependent upon intermittent delivery of luteinizing hormone-releasing hormone (LHRH) to the anterior pituitary. This mode of secretion is required to sensitize maximally the gonadotrophs to LHRH stimulation and to regulate gonadot ... Full text Link to item Cite

Tissue and cellular distribution of the extended family of protein kinase C isoenzymes.

Journal Article J Cell Biol · April 1992 Polyclonal isoenzyme-specific antisera were developed against four calcium-independent protein kinase C (PKC) isoenzymes (delta, epsilon, epsilon', and zeta) as well as the calcium-dependent isoforms (alpha, beta I, beta II, and gamma). These antisera show ... Full text Link to item Cite

Gonadotropin-releasing hormone neuronal cell lines.

Journal Article Front Neuroendocrinol · April 1992 Gonadotropin-releasing hormone (GnRH) cell lines were developed by genetically targeted tumorigenesis in transgenic mice. The cell lines designated GT1 cells have a neuronal phenotype, express neuronal but not glial markers and express the GnRH gene at hig ... Link to item Cite

Selective changes in protein kinase C isoenzymes in rat liver nuclei during liver regeneration.

Journal Article Biochem Biophys Res Commun · February 14, 1992 Using isoenzyme-specific antisera, protein kinase C (PKC) alpha and PKC delta were detected in total liver homogenate and in isolated nuclei. PKC beta I, beta II, epsilon, epsilon', and zeta were not detected. During liver regeneration, nuclear PKC alpha l ... Full text Link to item Cite

Immortalized hypothalamic gonadotropin-releasing hormone neurons.

Journal Article Ciba Found Symp · 1992 The neuroendocrine hypothalamus has been intensively studied using whole animals and tissue slices. However, it has been difficult to approach questions at the molecular and cellular level. By targeting expression of the oncogene product, simian virus 40 T ... Full text Link to item Cite

Morphological characterization of immortalized hypothalamic neurons synthesizing luteinizing hormone-releasing hormone.

Journal Article Endocrinology · September 1991 An immortalized LHRH cell line has recently been developed by genetically targeting these neurons for tumorigenesis. One of the subclones, the GT1-7 cells, was characterized at both the light and electron microscopic levels to study the cellular and subcel ... Full text Link to item Cite

Metabolism of pro-luteinizing hormone-releasing hormone in immortalized hypothalamic neurons.

Journal Article Endocrinology · September 1991 An immortalized hypothalamic neuronal cell line was recently developed by genetically targeting the expression of the simian virus-40 large T-antigen in LHRH neurons. These GT1 cells were subcloned to GT1-1, GT1-3, and GT1-7 cells, and they have been shown ... Full text Link to item Cite

Role of angiotensin II and vasopressin in cisplatin-induced emesis.

Journal Article Life Sci · 1990 Cisplatin-containing chemotherapy regimens are known to produce intense nausea and vomiting. Angiotensin II (AII) and vasopressin (AVP) have been shown to have emetic properties. The role of these two peptides on cisplatin-induced vomiting was investigated ... Full text Link to item Cite

Testosterone selectively influences protein kinase-C-coupled secretion of proluteinizing hormone-releasing hormone-derived peptides.

Journal Article Endocrinology · July 1989 LHRH and GnRH-associated peptide (GAP) are two major pro-LHRH-derived peptides which are secreted from median eminence (ME) nerve terminals in vitro. The purpose of the present experiment was to determine whether manipulation of gonadal steroid levels in v ... Full text Link to item Cite

Combined antibody-high-performance liquid chromatography approach to assess prohormone processing.

Journal Article Methods Enzymol · 1989 Full text Link to item Cite

Processing of the luteinizing hormone-releasing hormone precursor in the preoptic area and hypothalamus of the rat.

Journal Article Mol Endocrinol · January 1988 The LHRH precursor is known to contain the decapeptide and a 56 amino acid peptide termed gonadotropin-releasing hormone-associated peptide (GAP). The purpose of our study was to characterize the proLHRH and its processed products from the cell body and fi ... Full text Link to item Cite

Differential secretion of proLHRH fragments in response to [K+], prostaglandin E2 and C kinase activation.

Journal Article Mol Cell Endocrinol · January 1988 ProLHRH contains the luteinizing hormone-releasing hormone (LHRH) decapeptide and a 56 amino acid peptide designated gonadotropin-releasing hormone-associated peptide (GAP). We studied the effects of various known secretagogues of LHRH on the in vitro rele ... Full text Link to item Cite

In vivo biosynthesis of arginine vasopressin and oxytocin in hypothalami from intact and hypophysectomized rats.

Journal Article Endocrinology · June 1987 The rates of incorporation of [35S]cysteine into arginine vasopressin (AVP) and oxytocin (OXT) were studied concurrently in hypothalami from intact and hypophysectomized male rats. After label injection into the third ventricle, rats were killed 0.5, 1, 2, ... Full text Link to item Cite

Orchidectomy induces temporal and regional changes in the synthesis and processing of the LHRH prohormone in the rat brain.

Journal Article Adv Exp Med Biol · 1987 Full text Link to item Cite

Effect of hypophysectomy on somatostatin-14 and somatostatin-28 biosynthesis in the rat hypothalamus.

Journal Article Brain Res · April 9, 1986 The in vivo incorporation of [35S]cysteine into hypothalamic somatostatin-28 was found to be substantially below normal in hypophysectomized rats. A smaller reduction in label incorporation into arginine vasopressin was also observed, while incorporation i ... Full text Link to item Cite

Hepatic prolactin binding in female Sprague-Dawley rats fed a diet high in corn oil.

Journal Article J Natl Cancer Inst · August 1984 The relationship between dietary fat content and hepatic prolactin (PRL) binding during the four stages of the estrous cycle was examined. Serum 17 beta-estradiol, PRL, and progesterone were also monitored in the same animals. Female SD rats were fed 5 or ... Full text Link to item Cite

Absence of an effect of dietary corn oil content on plasma prolactin, progesterone, and 17 beta-estradiol in female Sprague-Dawley rats.

Journal Article Cancer Res · April 1984 Enhancement of mammary tumorigenesis in rats by high-fat diets has been postulated to be due to altered hormonal status. Elevated serum prolactin and, in some cases, estrogen have been reported in rats fed diets high in corn oil or lard that increase 7,12- ... Link to item Cite

Hepatic prolactin binding in female rats fed control or high corn oil diets

Journal Article Federation Proceedings · January 1, 1984 Cite

Mammary carcinogenesis in rats fed different amounts and types of fat.

Journal Article Cancer Res · September 1981 Link to item Cite

Mammary Carcinogenesis In Rats Fed Different Amounts And Types Of Fat

Journal Article Cancer Research · September 1, 1981 Rats fed 20% corn oil or lard showed increased 7,12-di-methylbenzanthracene-induced mammary tumorigenesis and slightly increased growth rate compared to rats fed 5% fat; 20% corn oil accelerated sexual maturation, but 20% lard did not. In contrast, diets h ... Cite

Dietary fat and DMBA mammary carcinogenesis in rats.

Journal Article Cancer Detect Prev · 1981 While there is no convincing direct evidence of an influence of specific dietary factors on breast cancer in women, the overall geographic correlation between risk of breast cancer and food consumption patterns suggests a positive link. Epidemiologic studi ... Link to item Cite

Effect of dietary fat on mammary carcinogenesis and serum prolactin in rats

Journal Article Federation Proceedings · January 1, 1980 Cite

Pressure influences on air-licking behavior of rats

Journal Article Physiological Psychology · January 1, 1978 In an effort to resolve a paradox posed by conflicting speculations about pressure influences on air-licking, two experiments examined this performance in thirsty rats as a consequence of manipulation of the pressure of a delivered air stream. The first ex ... Full text Cite

Some characteristics of concurrent discrimination and retention by monkeys

Journal Article Learning and Motivation · January 1, 1977 Before and after learning-set training, 12 rhesus monkeys were tested on the acquisition and retention of tasks consisting of eight concurrent object discrimination problems. Training on the concurrent discrimination was administered unitil a fairly string ... Full text Cite

Effects of artificial rewarming upon hypothermia-induced retrograde amnesia

Journal Article Physiological Psychology · January 1, 1976 Three experiments were conducted to examine the relationship between recovery rate from deep body cooling and later memory loss. In each of these three investigations, a passive avoidance trial was followed immediately by hypothermia and recovery was manip ... Full text Cite