Scholars@Duke
Carol Anne Colton

Carol Anne Colton

Professor in Neurology
Neurology, Behavioral Neurology
carol.colton@duke.edu
Duke Box 2900, Durham, NC 27710
201H Bryan Res Bldg, Durham, NC 27710

Selected Publications

Alzheimer's Disease Protein Relevance Analysis Using Human and Mouse Model Proteomics Data.

Journal Article Front Syst Biol · 2023 The principles governing genotype-phenotype relationships are still emerging(1-3), and detailed translational as well as transcriptomic information is required to understand complex phenotypes, such as the pathogenesis of Alzheimer's disease. For this reas ... Full text Link to item Cite

Infection and inflammation: New perspectives on Alzheimer's disease.

Journal Article Brain Behav Immun Health · July 2022 Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ... Full text Link to item Cite

Absolute Winding Number Differentiates Mouse Spatial Navigation Strategies With Genetic Risk for Alzheimer's Disease.

Journal Article Front Neurosci · 2022 Spatial navigation and orientation are emerging as promising markers for altered cognition in prodromal Alzheimer's disease, and even in cognitively normal individuals at risk for Alzheimer's disease. The different APOE gene alleles confer various degrees ... Full text Link to item Cite

Corrigendum: Absolute winding number differentiates mouse spatial navigation strategies with genetic risk for Alzheimer's disease.

Journal Article Front Neurosci · 2022 [This corrects the article DOI: 10.3389/fnins.2022.848654.]. ... Full text Link to item Cite

Percutaneous vagus nerve stimulation modulates glia activity and rescues acute Aβ deposition in a mouse model of delirium superimposed on dementia

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: Millions of Americans live with Alzheimer's disease (AD) and routinely require common surgical interventions, such as orthopedic surgery. However, these potentially life-saving procedures often increase the risk for further cognitive complicati ... Full text Cite

CVN-AD Alzheimer's mice show premature reduction in neurovascular coupling in response to spreading depression and anoxia compared to aged controls.

Journal Article Alzheimers Dement · July 2021 We compared the efficacy of neurovascular coupling and substrate supply in cerebral cortex during severe metabolic challenges in transgenic Alzheimer's [CVN-AD] and control [C57Bl/6] mice, to evaluate the hypothesis that metabolic insufficiency is a critic ... Full text Link to item Cite

Capillary Electrophoresis-High Resolution Mass Spectrometry for Measuring In Vivo Arginine Isotope Incorporation in Alzheimer's Disease Mouse Models.

Journal Article J Am Soc Mass Spectrom · June 2, 2021 Immune-based metabolic reprogramming of arginine utilization in the brain contributes to the neuronal pathology associated with Alzheimer's disease (AD). To enable our long-term goals of differentiation of AD mouse model genotypes, ages, and sexes based on ... Full text Open Access Link to item Cite

Likelihood ratio statistics for gene set enrichment in Alzheimer's disease pathways.

Journal Article Alzheimers Dement · April 2021 INTRODUCTION: The study of Alzheimer's disease (AD) has revealed biological pathways with implications for disease neuropathology and pathophysiology. These pathway-level effects may also be mediated by individual characteristics or covariates such as age ... Full text Link to item Cite

Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.

Journal Article ASN Neuro · 2021 Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-media ... 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

Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics.

Journal Article J Proteome Res · April 3, 2020 Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method dev ... Full text Link to item Cite

Vascular Cellular Adhesion Molecule-1 (VCAM-1) and Memory Impairment in African-Americans after Small Vessel-Type Stroke.

Journal Article J Stroke Cerebrovasc Dis · April 2020 BACKGROUND: African-Americans (AA) are 3 times more likely to have small-vessel-type ischemic strokes (SVS) than Whites. Small vessel strokes are associated with cognitive impairment, a relationship incompletely explained by white matter hyperintensity (WM ... Full text Link to item Cite

Novel LRRK2 Transgenic Mouse Model to Understand Gene x Environment Interactions.

Conference ENVIRONMENTAL AND MOLECULAR MUTAGENESIS · 2020 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

Identifying Vulnerable Brain Networks in Mouse Models of Genetic Risk Factors for Late Onset Alzheimer's Disease.

Journal Article Front Neuroinform · 2019 The major genetic risk for late onset Alzheimer's disease has been associated with the presence of APOE4 alleles. However, the impact of different APOE alleles on the brain aging trajectory, and how they interact with the brain local environment in a sex s ... Full text Link to item Cite

Speaking out about gender imbalance in invited speakers improves diversity.

Journal Article Nat Immunol · April 18, 2017 Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committee ... Full text Link to item Cite

Role of free radicals in alcohol-induced tissue injury

Chapter · January 1, 2017 The role of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) in ethanol-induced toxicity has been supported by a variety of in vivo and in vitro studies. All tissues in the body are affected by exposure to ethanol, and variatio ... Full text 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

The effects of the apoE4 genotype on the developing mouse retina.

Journal Article Exp Eye Res · April 2016 Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. The retina, which is as an extension of the central nervous system (CNS), is a particularly suitable model ... Full text Link to item Cite

Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke.

Journal Article Transl Stroke Res · December 2015 The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflamma ... Full text Link to item Cite

Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease.

Journal Article J Neurosci · April 15, 2015 The pathogenesis of Alzheimer's disease (AD) is a critical unsolved question; and although recent studies have demonstrated a strong association between altered brain immune responses and disease progression, the mechanistic cause of neuronal dysfunction a ... Full text Link to item Cite

The impact of human and mouse differences in NOS2 gene expression on the brain's redox and immune environment.

Journal Article Mol Neurodegener · November 17, 2014 BACKGROUND: Mouse models are used in the study of human disease. Despite well-known homologies, the difference in immune response between mice and humans impacts the application of data derived from mice to human disease outcomes. Nitric oxide synthase-2 ( ... Full text Link to item Cite

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

Journal Article J Neuropathol Exp Neurol · August 2014 Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that ... Full text Link to item Cite

Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase.

Journal Article J Proteome Res · October 4, 2013 Alzheimer's disease (AD) is a complex neurodegenerative process that involves altered brain immune, neuronal and metabolic functions. Understanding the underlying mechanisms has relied on mouse models that mimic components of AD pathology. We used gel-free ... Full text Link to item Cite

Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer's disease that exhibit neurodegeneration.

Journal Article Biomed Spectrosc Imaging · April 1, 2013 BACKGROUND: In Alzheimer's disease (AD), alterations in metal homeostasis, including the accumulation of metal ions in the plaques and an increase of iron in the cortex, have been well documented but the mechanisms involved are poorly understood. OBJECTIVE ... Full text Link to item Cite

Immune heterogeneity in neuroinflammation: dendritic cells in the brain.

Journal Article J Neuroimmune Pharmacol · March 2013 Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment ... Full text Link to item Cite

Microglial-neuronal interactions during neurodegenerative diseases.

Journal Article J Neuroimmune Pharmacol · March 2013 The impact of the brain's immune response to disease is no longer relegated to a secondary event of limited interest. Multiple types of brain and spinal cord injuries and diseases show varying immune phenotypes over the time course of the disease. The coll ... Full text Link to item Cite

Nitric oxide-mediated regulation of β-amyloid clearance via alterations of MMP-9/TIMP-1.

Journal Article J Neurochem · December 2012 Fibrillar amyloid plaques are largely composed of amyloid-beta (Aβ) peptides that are metabolized into products, including Aβ1-16, by proteases including matrix metalloproteinase 9 (MMP-9). The balance between production and degradation of Aβ proteins is c ... Full text Link to item Cite

Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype.

Journal Article PLoS One · 2012 Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau patholo ... Full text Link to item Cite

APOE-mimetic peptides reduce behavioral deficits, plaques and tangles in Alzheimer's disease transgenics.

Journal Article Neurodegener Dis · 2012 BACKGROUND: After age, the second largest risk factor for Alzheimer's disease (AD) is apolipoprotein E (APOE) genotype, where APOE4 is associated with lower apoE protein levels, more severer brain pathology, enhanced inflammation and disease. Small peptide ... Full text Link to item Cite

Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.

Journal Article J Alzheimers Dis · 2012 Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where the ε4 allele increases and the ε2 allele decreases the risk for developing disease. Specific mutations within the amyloid-β ... Full text Link to item Cite

Anti-amyloid-β immunotherapy in Alzheimer's disease: Relevance of transgenic mouse studies to clinical trials

Journal Article Advances in Alzheimer's Disease · December 1, 2011 Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the amyloid-β peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in the ... Full text Cite

Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses.

Journal Article ASN Neuro · November 30, 2011 Featured Publication While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully charac ... Full text Link to item Cite

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies.

Journal Article Alzheimers Res Ther · September 28, 2011 Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve be ... Full text Link to item Cite

Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence.

Journal Article J Neuroinflammation · September 9, 2011 BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of m ... Full text Link to item Cite

Nitric oxide and redox mechanisms in the immune response.

Journal Article J Leukoc Biol · June 2011 Featured Publication The role of redox molecules, such as NO and ROS, as key mediators of immunity has recently garnered renewed interest and appreciation. To regulate immune responses, these species trigger the eradication of pathogens on the one hand and modulate immunosuppr ... Full text Link to item Cite

Apolipoprotein E and peptide mimetics modulate inflammation by binding the SET protein and activating protein phosphatase 2A.

Journal Article J Immunol · February 15, 2011 The molecular mechanism by which apolipoprotein E (apoE) suppresses inflammatory cytokine and NO production is unknown. Using an affinity purification approach, we found that peptide mimetics of apoE, derived from its receptor binding domain residues 130-1 ... Full text Link to item Cite

Enhanced capillary amyloid angiopathy-associated pathology in Tg-SwDI mice with deleted nitric oxide synthase 2.

Journal Article Stroke · October 2010 Featured Publication BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy Type 1 is characterized by amyloid β protein deposition along cerebral capillaries and is accompanied by perivascular neuroinflammation and accumulation of phospho-tau protein. Tg-SwDI mice recapitulate c ... Full text Link to item Cite

An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.

Journal Article J Pharmacol Exp Ther · July 2010 Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRL ... Full text Link to item Cite

Assessing activation states in microglia.

Journal Article CNS Neurol Disord Drug Targets · April 2010 Featured Publication Since the original identification of microglia as a principal player in the brain's innate immune response, microglial activation has been widely studied. Recent studies suggest that microglial responses are heterogeneous, requiring a more precise definiti ... Full text Link to item Cite

Interaction of NG2(+) glial progenitors and microglia/macrophages from the injured spinal cord.

Journal Article Glia · March 2010 Spinal cord contusion produces a central lesion surrounded by a peripheral rim of residual white matter. Despite stimulation of NG2(+) progenitor cell proliferation, the lesion remains devoid of normal glia chronically after spinal cord injury (SCI). To in ... Full text Link to item Cite

Heterogeneity of microglial activation in the innate immune response in the brain.

Journal Article J Neuroimmune Pharmacol · December 2009 Featured Publication The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain's innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, ... Full text Link to item Cite

APOE genotype-specific differences in the innate immune response.

Journal Article Neurobiol Aging · September 2009 Featured Publication Apolipoprotein-E protein is an endogenous immunomodulatory agent that affects both the innate and the adaptive immune responses. Since individuals with the APOE4 gene demonstrate worsened pathology and poorer outcomes in many neurological disorders, we exa ... Full text Link to item Cite

Amyloid reduction by amyloid-beta vaccination also reduces mouse tau pathology and protects from neuron loss in two mouse models of Alzheimer's disease.

Journal Article J Neurosci · June 24, 2009 Featured Publication Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). Due to limitations in available animal models, however, it has been unclea ... Full text Link to item Cite

Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease.

Journal Article Neuroscience · March 31, 2009 Featured Publication The neurovascular unit (NVU) comprises cerebral blood vessels and surrounding astrocytes, neurons, perivascular microglia and pericytes. Astrocytes associated with the NVU are responsible for maintaining cerebral blood flow and ionic and osmotic balances i ... Full text Link to item Cite

Immunotherapy, vascular pathology, and microhemorrhages in transgenic mice.

Journal Article CNS Neurol Disord Drug Targets · March 2009 Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that results in severe cognitive decline. Amyloid plaques are a principal pathology found in AD and are composed of aggregated amyloid-beta (Abeta) peptides. According to the amyloid hyp ... Full text Link to item Cite

The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.

Journal Article Neurobiol Aging · December 2008 Featured Publication The apolipoprotein E4 (APOE4) gene is a well-known risk factor for Alzheimer's disease (AD) and other neurological disorders. Post-menopausal women with AD who express at least one APOE4 gene have more severe neuropathology and worsened cognitive scores th ... Full text Link to item Cite

Anti-amyloid-beta immunotherapy in Alzheimer's disease: relevance of transgenic mouse studies to clinical trials.

Journal Article J Alzheimers Dis · December 2008 Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the amyloid-beta peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in ... Full text Link to item Cite

The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP.

Journal Article J Alzheimers Dis · December 2008 Featured Publication Nitric oxide synthase 2 (NOS2) and its gene product, inducible NOS (iNOS) play an important role in neuroinflammation by generating nitric oxide (NO), a critical signaling and redox factor in the brain. Although NO is associated with tissue damage, it can ... Full text Link to item Cite

The chemical biology of nitric oxide: implications in cellular signaling.

Journal Article Free Radic Biol Med · July 1, 2008 Nitric oxide (NO) has earned the reputation of being a signaling mediator with many diverse and often opposing biological activities. The diversity in response to this simple diatomic molecule comes from the enormous variety of chemical reactions and biolo ... Full text Link to item Cite

Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice.

Journal Article J Neurosci · May 14, 2008 Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA). Specific mutations within the amyloid-beta protein (Abeta) peptide have been identified that cause familial forms of CAA. However, ... Full text Link to item Cite

Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2.

Journal Article J Neurosci · February 13, 2008 Featured Publication Alzheimer's disease (AD) is characterized by three primary pathologies in the brain: amyloid plaques, neurofibrillary tangles, and neuron loss. Mouse models have been useful for studying components of AD but are limited in their ability to fully recapitula ... Full text Link to item Cite

Quantitative measurement of postural sway in mouse models of human neurodegenerative disease.

Journal Article Neuroscience · September 21, 2007 Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a center of pressure (CoP) assay in mice to quantify postural sway produced by genetic ... Full text Link to item Cite

NOS2 in chronic neurodegeneration: Protection not damage

Conference JOURNAL OF NEUROCHEMISTRY · August 1, 2007 Link to item Cite

Androgen-mediated immune function is altered by the apolipoprotein E gene.

Journal Article Endocrinology · July 2007 Featured Publication Androgens, like estrogens, have been linked to neuroprotective effects in the brain and to the improvement of cognitive function. Part of this effect may be due to the action of androgens on the innate immune response. We have examined the action of dihydr ... Full text Link to item Cite

Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD.

Journal Article J Neuroinflammation · September 27, 2006 Featured Publication BACKGROUND: Microglia are associated with neuritic plaques in Alzheimer disease (AD) and serve as a primary component of the innate immune response in the brain. Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide fragments (Abeta) o ... Full text Link to item Cite

Advancing the study of stroke in women: summary and recommendations for future research from an NINDS-Sponsored Multidisciplinary Working Group.

Journal Article Stroke · September 2006 BACKGROUND AND PURPOSE: Women have poorer outcomes from stroke than men. Women also have risk factors that are unique, including pregnancy and hormone therapy. Hormone therapy for postmenopausal replacement increased the risk of ischemic stroke according t ... Full text Link to item Cite

Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in a murine model of multiple sclerosis.

Journal Article J Pharmacol Exp Ther · September 2006 Apolipoprotein E (apoE), well known to play a role in lipid transport and cholesterol metabolism, also exerts anti-inflammatory and neuroprotective effects in the central nervous system. Recent clinical and genetic studies display an association between ap ... Full text Link to item Cite

NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease.

Journal Article Proc Natl Acad Sci U S A · August 22, 2006 Featured Publication Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelatio ... Full text Link to item Cite

Characterization of NO and cytokine production in immune-activated microglia and peritoneal macrophages derived from a mouse model expressing the human NOS2 gene on a mouse NOS2 knockout background.

Journal Article Antioxid Redox Signal · 2006 Featured Publication Significant differences exist in the production and release of nitric oxide (NO) from human macrophages versus macrophages of mouse origin. Human macrophages have been shown to respond poorly to stimuli that provoke strong inflammatory reactions from mouse ... Full text Link to item Cite

Oxidation and CBS in neural derived cells

Conference FREE RADICAL BIOLOGY AND MEDICINE · January 1, 2006 Link to item Cite

Y+ and y+ L arginine transporters in neuronal cells expressing tyrosine hydroxylase.

Journal Article Biochim Biophys Acta · August 15, 2005 Featured Publication Arginine is a semi-essential amino acid that serves as sole substrate for enzymes involved in diverse cell processes including redox balance via nitric oxide synthase (NOS) and cell proliferation via arginase. Neurons that express nNOS require intracellula ... Full text Link to item Cite

Sex steroids, APOE genotype and the innate immune system.

Journal Article Neurobiol Aging · March 2005 Microglia are a primary cellular component of the CNS innate immune system. Their response to conserved pathogen motifs is inherent and leads to the release of cytoactive factors that impact surrounding neurons and glia. The microglial response is modified ... Full text Link to item Cite

Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.

Journal Article J Neurosci · August 11, 2004 Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of ... Full text Link to item Cite

Nitric oxide production and regulation of neuronal NOS in tyrosine hydroxylase containing neurons.

Journal Article Exp Neurol · August 2004 CAD cells are a murine CNS catecholaminergic (tyrosine hydroxylase-positive; TH+) neuronal cell line that undergoes morphological differentiation to resemble CNS catecholaminergic neurons upon serum deprivation. We show here that CAD cells also express neu ... Full text Link to item Cite

APOE genotype-specific differences in human and mouse macrophage nitric oxide production.

Journal Article J Neuroimmunol · February 2004 Individuals expressing an APOE4 genotype demonstrate increased Alzheimer's disease (AD) neuropathology and a decreased onset age. The APOE4 gene may act by modulating the CNS immune response. Using human monocyte-derived macrophages (MDM), we show a signif ... Full text Link to item Cite

Orthogonal properties of the redox siblings nitroxyl and nitric oxide in the cardiovascular system: a novel redox paradigm.

Journal Article Am J Physiol Heart Circ Physiol · December 2003 Endogenous formation of nitric oxide (NO) and related nitrogen oxides in the vascular system is critical to regulation of multiple physiological functions. An imbalance in the production or availability of these species can result in progression of disease ... Full text Link to item Cite

Redox regulation of neuronal migration in a Down Syndrome model.

Journal Article Free Radic Biol Med · September 15, 2003 Down Syndrome (DS), one of the major genetic causes of mental retardation, is characterized by disrupted corticogenesis produced, in part, by an abnormal layering of neurons in cortical laminas II and III. Because defects in the normal migration of neurons ... Full text Link to item Cite

Compartmentalized nitrosation and nitration in mitochondria.

Journal Article Antioxid Redox Signal · June 2003 A wide spectrum of the biological actions of nitric oxide and its oxidizing metabolites are mediated via mitochondria. Mitochondria are highly compartmentalized organelles consisting of three distinct compartments: the matrix, the intermembrane space, and ... Full text Link to item Cite

Mitochondria and nitric oxide.

Journal Article Antioxid Redox Signal · June 2003 Full text Link to item Cite

Heme proteins and nitric oxide (NO): the neglected, eloquent chemistry in NO redox signaling and regulation.

Journal Article Antioxid Redox Signal · June 2003 The role of nitric oxide (NO) in cellular physiology and signaling has been an important aspect in biomedical science over the last decade. As NO is a small uncharged radical, the chemistry of NO within the redox environment of the cell dictates the majori ... Full text Link to item Cite

A humanized NOS2 transgenic mouse

Conference FASEB JOURNAL · March 14, 2003 Link to item Cite

Microglial function in human APOE3 and APOE4 transgenic mice: altered arginine transport.

Journal Article J Neuroimmunol · January 2003 The APOE4 genotype is a known risk factor for Alzheimer's disease (AD) and is associated with poorer outcomes after neuropathological insults. To understand APOE's function, we have examined microglia, the CNS specific macrophage, in transgenic mice expres ... Full text Link to item Cite

Apolipoprotein E isoform mediated regulation of nitric oxide release.

Journal Article Free Radic Biol Med · June 1, 2002 Progressive dysfunction and death of neurons in Alzheimer's dementia is enhanced in patients carrying one or more APOE4 alleles who also display increased presence of oxidative stress markers. Modulation of oxidative stress is a nontraditional and physiolo ... Full text Link to item Cite

Further evidence for distinct reactive intermediates from nitroxyl and peroxynitrite: effects of buffer composition on the chemistry of Angeli's salt and synthetic peroxynitrite.

Journal Article Arch Biochem Biophys · May 15, 2002 The nitroxyl (HNO) donor Angeli's salt (Na(2)N(2)O(3); AS) is cytotoxic in vitro, inducing double strand DNA breaks and base oxidation, yet may have pharmacological application in the treatment of cardiovascular disease. The chemical profiles of AS and syn ... Full text Link to item Cite

Apolipoprotein-E allele-specific regulation of nitric oxide production.

Journal Article Ann N Y Acad Sci · May 2002 Cognitive decline and dementia are key features of Alzheimer's disease (AD) that result from failure of neuronal function. Affected neurons demonstrate indices of nitrosative stress resulting from changes in nitric oxide (NO) mediated redox balance. Neurof ... Full text Link to item Cite

APOE and the regulation of microglial nitric oxide production: a link between genetic risk and oxidative stress.

Journal Article Neurobiol Aging · 2002 The mechanism linking the APOE4 gene with increased susceptibility for Alzheimer's disease (AD) and poorer outcomes following closed head injury and stroke is unknown. One potential link is activation of the innate immune system in the CNS. Our previously ... Full text Link to item Cite

Nitroxyl anion regulation of the NMDA receptor.

Journal Article J Neurochem · September 2001 Nitric oxide (NO) is an important regulator of NMDA channel function in the CNS. Recent findings suggest that nitroxyl anion (NO(-)) may also be generated by nitric oxide synthase, which catalyzes production of NO. Using recombinant NMDA receptors (NMDA-r) ... Full text Link to item Cite

Mechanisms of the antioxidant effects of nitric oxide.

Journal Article Antioxid Redox Signal · April 2001 The Janus face of nitric oxide (NO) has prompted a debate as to whether NO plays a deleterious or protective role in tissue injury. There are a number of reactive nitrogen oxide species, such as N2O3 and ONOO-, that can alter critical cellular components u ... Full text Link to item Cite

Apolipoprotein E acts to increase nitric oxide production in macrophages by stimulating arginine transport.

Journal Article Biochim Biophys Acta · February 14, 2001 Previous studies have shown that apolipoprotein E (apoE) plays a role in immune function by modulating tissue redox balance. Using a mouse macrophage cell line (RAW 264.7), we have examined the mechanism by which apoE regulates nitric oxide (NO) production ... Full text Link to item Cite

In Memory of Daniel L. Gilbert – A Radical Spirit

Journal Article Antioxidants and Redox Signaling · February 1, 2001 Full text Cite

Microglial contribution to oxidative stress in Alzheimer's disease.

Journal Article Ann N Y Acad Sci · 2000 Microglia are the CNS macrophage and are a primary cellular component of plaques in Alzheimer's disease (AD) that may contribute to the oxidative stress associated with chronic neurodegeneration. We now report that superoxide anion production in microglia ... Full text Link to item Cite

Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death.

Journal Article Am J Physiol · October 1999 Nitric oxide (NO) released from a new chemical class of donors enhances N-methyl-D-aspartate (NMDA) channel activity. Using whole cell and single-channel patch-clamp techniques, we have shown that (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]-NO (PAPA-NO) ... Full text Link to item Cite

Function of microglia in organotypic slice cultures.

Journal Article J Neurosci Res · June 15, 1999 We have examined the functional characteristics of microglia in an environment where the cytoarchitecture of the brain is preserved. Using organotypic slice culture under serum-free conditions, microglia initially demonstrated a rounded morphology but afte ... Full text Link to item Cite

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration.

Journal Article J Neurosci · June 1, 1999 During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, G ... Full text Link to item Cite

Ethanol induced changes in superoxide anion and nitric oxide in cultured microglia.

Journal Article Alcohol Clin Exp Res · May 1998 Induction of oxidative stress has been implicated as a causative factor in fetal alcohol syndrome although the source of reactive oxygen species is not clear. One potential source is the microglia, the CNS macrophage, which generate superoxide anion as par ... Link to item Cite

Apolipoprotein E enhances nitric oxide production in Poly I:Poly C-treated RAW (264.7) cells

Journal Article FASEB Journal · 1998 It has been reported that apolipoprotein E may be associated with the oxidative stress induced during chronic neurodegenerative diseases. We have previously reported that the polyribonucleotide, PolyI:C, enhances nitric oxide production in apoE treated hum ... Cite

Phagocytosis of rod outer membrane segments by human retinal pigment epithelial cells increases nitric oxide production

Journal Article FASEB Journal · 1998 Retinal pigment epithelial cells (RPE) are involved in the maintenance of normal photoreceptor cells in the retina by phagocytosis of spent rod and cone outer membrane segments. RPE cells demonstrate other macrophagic characteristics including the expressi ... Cite

Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.

Journal Article Biochem Biophys Res Commun · November 17, 1997 Induction of oxidative stress has been implicated as a causative factor in chronic neurodegenerative diseases such as Alzheimer's disease. Apolipoprotein-E (apoE) and amyloid-beta peptide (A beta) have been reported to alter the redox state of the brain. U ... Full text Link to item Cite

Polyribonucleotides induce nitric oxide production by human monocyte-derived macrophages.

Journal Article J Leukoc Biol · September 1997 Cytokine-mediated activation of inducible nitric oxide synthase (iNOS) in monocytes or macrophages is species specific. In contrast to rat or mouse, human macrophages do not produce measurable levels of nitric oxide (NO) when induced by inflammatory mediat ... Full text Link to item Cite

Activated human microglia produce the excitotoxin quinolinic acid.

Journal Article Neuroreport · January 20, 1997 We aimed to determine the relative role of quinolinic acid synthesis in purified human microglia, monocyte-derived macrophages and astrocytes in the human brain following immune stimulation. Microglia and macrophages significantly increased quinolinic acid ... Full text Link to item Cite

Biological activity of interleukin-10 in the central nervous system.

Journal Article Neurochem Int · 1997 Cytokines play a crucial role as mediators of inflammation. Astrocytes and microglia are the two major glial cells involved in the central nervous system immune responses. In this study we examined the effects of interleukin-10 (IL-10), one of the naturall ... Full text Link to item Cite

The induction of nitric oxide by polyribonucleotides in hamster and human glia

Journal Article FASEB Journal · December 1, 1996 Nitric oxide (NO), production by microglia and astrocytes is well characterized in cells isolated from rat or mouse CNS. However, notable differences in the levels of NO generated from both hamster and human glia have led us to examine the induction of nit ... Cite

Inhibition of microglial superoxide anion production by isoproterenol and dexamethasone.

Journal Article Neurochem Int · July 1996 Microglia, like other tissue macrophages, are a component of the hypothalamic-pituitary endocrine-immune axis and, as such, are responsive to both neural and endocrine factors. Using cultured neonatal hamster microglia, we have examined the effect of isopr ... Full text Link to item Cite

Location-dependent artifact for no measurement using multiwell plates.

Journal Article Free Radic Biol Med · 1996 The Griess reaction is widely used to measure the cellular production of NO by detecting the supernatant levels of nitrite. Ordinarily, background levels of nitrite in the media are subtracted from the levels of nitrite produced by the cells by preparing a ... Full text Link to item Cite

Species differences in the generation of reactive oxygen species by microglia.

Journal Article Mol Chem Neuropathol · 1996 Although a variety of potential sources for reactive oxygen species (ROS) exist in the CNS, brain macrophages, i.e., the microglia, generate large quantities of these reactive species, particularly in response to injury or inflammatory signals. In order to ... Full text Link to item Cite

The brain's immune system.

Journal Article Sci Am · November 1995 Full text Link to item Cite

Protection from oxidation enhances the survival of cultured mesencephalic neurons.

Journal Article Exp Neurol · March 1995 Oxidative stress has been linked to the destruction of dopaminergic neurons in the substantia nigra and may be a significant factor in both Parkinson's disease and MPTP toxicity. Using primary cultures of embryonic rat mesencephalon and standard immunocyto ... Full text Link to item Cite

K+ modulation of microglial superoxide production: involvement of voltage-gated Ca2+ channels.

Journal Article Am J Physiol · June 1994 A variety of cytoactive factors produced during injury and inflammation are known to activate the central nervous system (CNS) macrophage, the microglia. Since extracellular potassium levels are known to rise rapidly at sites of injury in the CNS, we exami ... Full text Link to item Cite

Microglial oxyradical production: causes and consequences.

Journal Article Neuropathol Appl Neurobiol · April 1994 Link to item Cite

Preface

Journal Article Annals of the New York Academy of Sciences · January 1, 1994 Full text Cite

GABA-induced chemokinesis and NGF-induced chemotaxis of embryonic spinal cord neurons.

Journal Article J Neurosci · January 1994 During CNS development, neuroblasts proliferate within germinal zones of the neuroepithelium, and then migrate to their final positions. Although many neurons are thought to migrate along processes of radial glial fibers, increasing evidence suggests envir ... Full text Link to item Cite

K+ modulation of microglial superoxide production: Involvement of voltage-gated Ca2+ channels

Journal Article American Journal of Physiology - Cell Physiology · 1994 A variety of cytoactive factors produced during injury and inflammation are known to activate the central nervous system (CNS) macrophage, the microglia. Since extracellular potassium levels are known to rise rapidly at sites of injury in the CNS, we exami ... Cite

Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation.

Journal Article J Neurosci Res · June 15, 1993 The production of collagen-degrading proteases by cultured neonatal rat microglia was examined using an immobilized fibronectin-gelatin matrix coupled to a fluorescent marker and by substrate gel analysis. When microglia were plated onto the surface of the ... Full text Link to item Cite

Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells.

Journal Article Peptides · 1993 Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of ... Full text Link to item Cite

Characterization of interleukin-1 production by microglia in culture.

Journal Article Brain Res · September 18, 1992 The production of interleukin-1 (IL-1) by cultured neonatal rat microglia was studied using the D10 cell assay. The results show that IL-1 was secreted in response to lipopolysaccharide (LPS) in a dose- and time-dependent fashion. IL-1 production was speci ... Full text Link to item Cite

Regulation of microglial function by interferons.

Journal Article J Neuroimmunol · September 1992 Cultured neonatal rat microglia were pretreated with varying doses of either purified interferon (IFN) alpha/beta or recombinant IFN gamma for 24 or 48 h and the following functional parameters examined; superoxide anion production, interleukin-1 secretion ... Full text Link to item Cite

Oxygen dependency of synaptic transmission at the squid Loligo pealei giant synapse.

Journal Article Comp Biochem Physiol Comp Physiol · June 1992 1. Synaptic transmission at the squid giant synapse was blocked in 45 min by exposure to 0.02 atm oxygen but was maintained for more than 90 min in air (0.21 atm oxygen) or pure oxygen (1 atm). 2. Excitatory post-synaptic potential amplitude decreased in 0 ... Full text Link to item Cite

Lectin staining of cultured CNS microglia.

Journal Article J Histochem Cytochem · April 1992 Carbohydrate binding proteins, known as lectins, bind to specific sugar groups on most membranes. We used fluorescent and light microscopy to study the interaction of various lectins with the membranes of microglia cultured from neonatal rat or fetal mouse ... Full text Link to item Cite

Abnormal production of interleukin-1 by microglia from trisomy 16 mice.

Journal Article Neurosci Lett · November 11, 1991 The production of interleukin-1 (IL-1) was examined in cultured CNS microglia obtained from trisomy 16 (Ts16) fetal mouse brain, a model system for studies relevant to Down syndrome (DS). When compared to microglia from their normal littermates, Ts16 micro ... Full text Link to item Cite

The effect of xanthine/xanthine oxidase generated reactive oxygen species on synaptic transmission.

Journal Article Free Radic Res Commun · 1991 The effect of reactive oxygen species generated by the interaction of xanthine and xanthine oxidase on synaptic transmission was examined at the squid giant synapse and the lobster neuromuscular junction. Exposure of these synaptic regions to xanthine/xant ... Full text Link to item Cite

Chemotaxis by a CNS macrophage, the microglia.

Journal Article J Neurosci Res · September 1990 Microglia demonstrate many characteristics similar to those seen in monocytes and tissue-specific macrophages, including phagocytosis, production of oxygen radicals, and growth factors and expression of MHC antigens. We have examined the ability of microgl ... Full text Link to item Cite

Effect of helium and heliox on glutamate decarboxylase activity.

Journal Article Undersea Biomed Res · July 1990 The activity of glutamate decarboxylase (GAD) in pure helium at 6.8 MPa was significantly enhanced when compared to GAD activity in air at 0.1 MPa (906 vs. 602 nmol.h-1.mg-1 protein, respectively). No significant difference was found between GAD activities ... Link to item Cite

Enhanced production of superoxide anion by microglia from trisomy 16 mice.

Journal Article Brain Res · June 11, 1990 Disruption of normal oxygen radical metabolism in the CNS may contribute to the neuropathological changes associated with Down syndrome (trisomy 21) and its mouse counterpart, the trisomy 16 (Ts16) mouse. One potent source of oxyradicals is the CNS-specifi ... Full text Link to item Cite

The action of hydrogen peroxide on paired pulse and long-term potentiation in the hippocampus.

Journal Article Free Radic Biol Med · 1989 The action of a reactive oxygen intermediate, that is, hydrogen peroxide (H2O2) on modulation of synaptic transmission was examined in the hippocampal brain slice preparation. Microinjection of H2O2 into the apical dendritic region of the CA1 pyramidal cel ... Full text Link to item Cite

Production of superoxide anions by a CNS macrophage, the microglia.

Journal Article FEBS Lett · November 2, 1987 Microglia have been implicated in both physiological and pathological processes of the brain. Their possible roles have been compared to those of macrophages and granulocytes. Here we demonstrate that specific ability of microglia to secrete the superoxide ... Full text Link to item Cite

Trigeminal responses to thermal stimulation of the oral cavity in rattlesnakes (Crotalus viridis) before and after bilateral anesthetization of the facial pit organs.

Journal Article Brain Res · January 6, 1987 Multiunit neural responses from the superficial maxillary branch of the trigeminal nerve in prairie rattlesnakes were elicited by intraoral thermal stimulation. The responses to oral stimulation were shown to be independent of responses obtained by thermal ... Full text Link to item Cite

The action of oxygen and oxygen at high pressure on inhibitory transmission.

Journal Article Brain Res · January 29, 1986 The effect of 100% oxygen at ambient pressure, 100% oxygen at 1.7 Atmospheres Absolute (ATA), 100% oxygen at 5.1 ATA, helium at 1.7 ATA and helium at 5.1 ATA on inhibitory synaptic transmission was studied using the lobster walking leg neuromuscular prepar ... Full text Link to item Cite

Changes in synaptic transmission produced by hydrogen peroxide.

Journal Article J Free Radic Biol Med · 1986 The effect of hydrogen peroxide (H2O2) on excitatory and inhibitory synaptic transmission was studied at the lobster neuromuscular junction. H2O2 produced a dose dependent decrease in the amplitude of the junction potential (Vejp). This decrease was due to ... Full text Link to item Cite

Blockade of hyperbaric oxygen induced seizures by excitatory amino acid antagonists.

Journal Article Can J Physiol Pharmacol · May 1985 The effectiveness of several excitatory amino acid antagonists to delay or block seizures induced by oxygen at high pressure was examined in mice. Of the antagonists tested, namely, L-proline, DL-alpha-aminoadipate, DL-2-amino-5-phosphonovalerate, and L-gl ... Full text Link to item Cite

Effect of H2O2 on excitatory transmission in the lobster neuromuscular junction

Journal Article Federation Proceedings · January 1, 1985 Cite

An electrophysiological analysis of oxygen and pressure on synaptic transmission.

Journal Article Brain Res · November 18, 1982 The effect of oxygen at high pressure (OHP), helium at 150 PSIG and 100% oxygen at ambient pressure on excitatory synaptic transmission was studied using the lobster walking leg neuromuscular preparation. Both 100% oxygen at 150 PSIG (7135 mm Hg oxygen) an ... Full text Link to item Cite

Effects of a thioreactive agent, diamide, on neuromuscular transmission in lobster.

Journal Article Am J Physiol · January 1982 Diamide[diazine-dicarboxylic acid-bis(dimethylamide)], a thiol-oxidizing agent, has both pre- and postsynaptic actions on the glutaminergic neuromuscular junction of the lobster walking leg. Postsynaptically, diamide produced an increase in the response to ... Full text Link to item Cite

Evaluation of a life support module used for air transport of critically ill infants.

Journal Article Aviat Space Environ Med · February 1979 To accomplish the safe transport of ill newborns, various infant transport systems have been developed. One such unit, produced by Airborne Life Support Systems, has been tested by the authors. The parameters used to evaluate the system were: (1) temperatu ... Link to item Cite

The action of dantrolene sodium on the lobster neuromuscular junction.

Journal Article Comp Biochem Physiol C Comp Pharmacol · 1979 Full text Link to item Cite

The action of dantrolene sodium on the lobster neuromuscular junction

Journal Article Comparative Biochemistry and Physiology. Part C, Comparative · 1979 1. At a concentration of 2.3 to 3.1 × 10-5 M, dantrolene Na increased the frequency of stimulation required to elicit a visible muscle contraction from 7 stimuli/sec to a minimum of 25 stimuli/sec. 2. At the same concentration, dantrolene Na had no effect ... Cite

Effect of oxygen at high pressure on spontaneous transmitter release

Journal Article American Journal of Physiology - Cell Physiology · December 1, 1978 The effect of oxygen at high pressure (OHP) on resting membrane properties [effective membrane resistance (R(eff)) and membrane potential (V(m))] and the spontaneous release of excitatory transmitter were examined at the lobster neuromuscular junction. Pre ... Cite

Effect of oxygen at high pressure on spontaneous transmitter release.

Journal Article Am J Physiol · November 1978 The effect of oxygen at high pressure (OHP) on resting membrane properties (effective membrane resistance (Reff) and membrane potential (Vm)) and the spontaneous release of excitatory transmitter were examined at the lobster neuromuscular junction. Pressur ... Full text Link to item Cite

Depression of glutamate-mediated synaptic transmission by benzyl alcohol.

Journal Article Can J Physiol Pharmacol · August 1977 The data obtained from this study suggest that the nonionizable anesthetic benzyl alcohol has two prominent actions on GABA- and glutamate-mediated synaptic transmission at the lobster neuromuscular junction. They are as follows: (1) depression of the exci ... Full text Link to item Cite

Oxygen microelectrode response to oxygen pressures up to 15 ATA.

Journal Article Aviat Space Environ Med · August 1976 Polarographic measurements of oxygen at high pressures were made at 21-22 degrees C with open-type Wood's metal microelectrodes with tip diameter about 5 mu. Although the sensitivity of the individual electrodes ranged from 3.1 x 10(-10) to 8.8 x 10(-12) a ... Link to item Cite

Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction.

Journal Article J Pharmacol Exp Ther · May 1976 The effects of the compounds 2-, 3- and 4-aminopyridine and sparteine on membrane conductance changes were examined using both voltage-clamped Myxicola axons and the lobster neuromuscular junction. In Myxicola axons, the aminopyridines very specifically in ... Link to item Cite

Dual response of lobster muscle fibers to L-glutamate.

Journal Article Comp Biochem Physiol C Comp Pharmacol · August 1, 1975 Full text Link to item Cite

La3+ blockage of glutamate action at the lobster neuromuscular junction.

Journal Article Comp Biochem Physiol C Comp Pharmacol · August 1, 1975 Full text Link to item Cite