Journal ArticleCurrent opinion in neurobiology · December 2024
A fundamental feature shared across neurodevelopmental disorders (NDDs) is the disruption of synaptic circuit formation and homeostasis. During early life, non-neuronal cells called astrocytes tightly regulate the establishment of circuits by controlling f ...
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Journal ArticlebioRxiv · October 10, 2024
CRISPR/Cas9-based genome engineering enables rapid and precise gene manipulations in the CNS. Here, we developed a non-invasive astrocyte-specific method utilizing a single AAV vector, which we named GEARBOCS (Gene Editing in AstRocytes Based On CRISPR/Cas ...
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Journal ArticleCell Rep Methods · September 16, 2024
The formation of precise numbers of neuronal connections, known as synapses, is crucial for brain function. Therefore, synaptogenesis mechanisms have been one of the main focuses of neuroscience. Immunohistochemistry is a common tool for visualizing synaps ...
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Journal ArticlebioRxiv · July 12, 2024
The formation of precise numbers of neuronal connections, known as synapses, is crucial for brain function. Therefore, synaptogenesis mechanisms have been one of the main focuses of neuroscience. Immunohistochemistry is a common tool for visualizing synaps ...
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Journal ArticleNeuron · May 15, 2024
Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis rem ...
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Journal ArticleCurr Opin Cell Biol · February 2024
Multiple Sclerosis (MS) is a common cause of impairment in working-aged adults. MS is characterized by neuroinflammation and infiltration of peripheral immune cells to the brain, which cause myelin loss and death of oligodendrocytes and neurons. Many studi ...
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Journal ArticleJ Cell Biol · November 6, 2023
Astrocytes control the formation of specific synaptic circuits via cell adhesion and secreted molecules. Astrocyte synaptogenic functions are dependent on the establishment of their complex morphology. However, it is unknown if distinct neuronal cues diffe ...
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Journal ArticleNat Commun · September 8, 2023
Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training ...
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Journal ArticleNat Commun · June 8, 2023
Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endo ...
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Journal ArticlebioRxiv · April 3, 2023
Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. To date, several astrocyte-secreted synaptogenic proteins controlling different stages of excitatory synapse development have been identified. However, the identitie ...
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Journal ArticleJCI Insight · December 8, 2022
High endothelial venule protein/SPARC-like 1 (hevin/Sparcl1) is an astrocyte-secreted protein that regulates synapse formation in the brain. Here we show that astrocytic hevin signaling plays a critical role in maintaining chronic pain. Compared with WT mi ...
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Journal ArticleCell Rep · August 2, 2022
Gestational exposure to environmental toxins and socioeconomic stressors is epidemiologically linked to neurodevelopmental disorders with strong male bias, such as autism. We model these prenatal risk factors in mice by co-exposing pregnant dams to an envi ...
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Journal ArticleGlia · August 2022
Brain circuits undergo substantial structural changes during development, driven by the formation, stabilization, and elimination of synapses. Synaptic connections continue to undergo experience-dependent structural rearrangements throughout life, which ar ...
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Journal ArticleSci Rep · July 13, 2022
Hevin is a secreted extracellular matrix protein that is encoded by the SPARCL1 gene. Recent studies have shown that Hevin plays an important role in regulating synaptogenesis and synaptic plasticity. Mutations in the SPARCL1 gene increase the risk of auti ...
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Journal ArticleNeuron · August 4, 2021
Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate ...
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Journal ArticleCurrent opinion in neurobiology · August 2021
A tripartite synapse comprises a neuronal presynaptic axon and a postsynaptic dendrite, which are closely ensheathed by a perisynaptic astrocyte process. Through their structural and functional association with thousands of neuronal synapses, astrocytes re ...
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Journal ArticleStructure · July 1, 2021
Astrocyte-secreted Hevin induces synapse formation by bridging the trans-synaptic organizers, neuroligins and neurexins. In this issue of Structure, Fan et al. (2021) elucidate the structural basis of Hevin's interaction with these molecules and reveal the ...
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Journal ArticleCell Rep · January 26, 2021
After spinal cord injury (SCI), normally innocuous visceral or somatic stimuli can trigger uncontrolled reflex activation of sympathetic circuitry, causing pathological dysautonomia. We show that remarkable structural remodeling and plasticity occur within ...
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Chapter · 2021
Astrocytes are the most abundant glial cells in the mammalian brain and directly participate in the proper functioning of the nervous system by regulating ion homeostasis, controlling glutamate reuptake, and maintaining the blood-brain barrier. In the last ...
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Journal ArticleHippocampus · December 2020
Analysis of long-term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L-LTP), lasting >3 hr, occurs abruptly at postnatal day 12 (P12) in the stratum radiatum of rat hippocampal area ...
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Journal ArticleNature · December 2020
Perisynaptic astrocytic processes are an integral part of central nervous system synapses1,2; however, the molecular mechanisms that govern astrocyte-synapse adhesions and how astrocyte contacts control synapse formation and function are largely unknown. H ...
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Journal ArticleCurr Opin Neurobiol · August 2020
Central nervous system function requires the proper formation and function of synapses. The α2δ auxiliary subunits of voltage-gated calcium channels have emerged as regulators of a number of critical events associated with regulation of synaptic function, ...
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Journal ArticleNeuron · April 8, 2020
The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines de ...
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Journal ArticleCell Rep · January 21, 2020
Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projec ...
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Chapter · January 1, 2020
Glial cells, particularly astrocytes, were once considered to be passive residents of nervous tissue, performing the most basic housekeeping functions such as spatial ion buffering and water homeostasis. However, in recent years, we have expanded our knowl ...
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Journal ArticleDev Cell · October 7, 2019
The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is ...
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Journal ArticleCurr Opin Neurobiol · August 2019
Neuroligins are a family of cell adhesion molecules, which are best known for their functions as postsynaptic components of the trans-synaptic neurexin-neuroligin complexes. Neuroligins are highly conserved across evolution with important roles in the form ...
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Journal ArticleNeuron · December 5, 2018
A key step in excitatory synapse maturation is the switch in AMPA receptor subunit composition to GluA2-containing calcium-impermeable receptors. Now, Blanco-Suarez et al. (2018) demonstrate that astrocyte-secreted chordin-like 1 drives this process, enabl ...
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Journal ArticleJ Cell Biol · October 1, 2018
Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP-α2δ-1 interaction is imp ...
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Journal ArticleJ Neurosci · March 21, 2018
Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidate ...
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Journal ArticleNeuron · January 3, 2018
Infections have been identified as possible risk factors for aging-related neurodegenerative diseases, but it remains unclear whether infection-related immune molecules have a causative role in neurodegeneration during aging. Here, we reveal an unexpected ...
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Journal ArticleNature · November 8, 2017
Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocy ...
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Journal ArticleNeuron · November 1, 2017
Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the es ...
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Journal ArticleCurr Opin Neurobiol · August 2017
Astrocytes are morphologically complex cells that perform a wide variety of critical functions in the brain. As a structurally and functionally integrated component of the synapse, astrocytes secrete proteins, lipids, and small molecules that bind neuronal ...
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Journal ArticleNat Commun · February 13, 2017
Huntington's Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription fa ...
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Journal ArticleCurr Opin Neurobiol · February 2017
In the brain, the formation of complex neuronal networks amenable to experience-dependent remodeling is complicated by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on neurons, but also non-neuronal gl ...
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Journal ArticleJ Biol Chem · June 17, 2016
Peripheral nerve injury induces increased expression of thrombospondin-4 (TSP4) in spinal cord and dorsal root ganglia that contributes to neuropathic pain states through unknown mechanisms. Here, we test the hypothesis that TSP4 activates its receptor, th ...
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Journal ArticleCell · January 14, 2016
Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of ...
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Journal ArticleAlcohol Clin Exp Res · December 2015
BACKGROUND: Adolescent intermittent alcohol exposure (AIE) has profound effects on neuronal function. We have previously shown that AIE causes aberrant hippocampal structure and function that persists into adulthood. However, the possible contributions of ...
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Journal ArticleJ Neurosci · November 25, 2015
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UNLABELLED: Cell therapy demonstrates great potential for the treatment of neurological disorders. Human umbilical tissue-derived cells (hUTCs) were previously shown to have protective and regenerative effects in animal models of stroke and retinal degener ...
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Journal ArticleAlcohol Clin Exp Res · June 2015
BACKGROUND: Human adolescence is a crucial stage of neurological development during which ethanol (EtOH) consumption is often at its highest. Alcohol abuse during adolescence may render individuals at heightened risk for subsequent alcohol abuse disorders, ...
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Journal ArticleCold Spring Harb Perspect Biol · February 6, 2015
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Astrocytes, through their close associations with synapses, can monitor and alter synaptic function, thus actively controlling synaptic transmission in the adult brain. Besides their important role at adult synapses, in the last three decades a number of c ...
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Journal ArticleElife · December 17, 2014
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During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. ...
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Journal ArticleJ Neurosci · July 9, 2014
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Huntington's disease (HD) is a neurodegenerative disease caused by the expansion of a poly-glutamine (poly-Q) stretch in the huntingtin (Htt) protein. Gain-of-function effects of mutant Htt have been extensively investigated as the major driver of neurodeg ...
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Journal ArticleBiol Psychiatry · April 15, 2014
BACKGROUND: Synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3) is an excitatory postsynaptic protein implicated in the pathogenesis of obsessive-compulsive behaviors. In mice, genetic deletion of Sapap3 causes obses ...
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Journal ArticlePLoS One · 2014
Dendritic spines are the primary recipients of excitatory synaptic input in the brain. Spine morphology provides important information on the functional state of ongoing synaptic transmission. One of the most commonly used methods to visualize spines is Go ...
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Journal ArticleSci Signal · July 9, 2013
Autism is a common and heritable neuropsychiatric disorder that can be categorized into two types: syndromic and nonsyndromic, the former of which are associated with other neurological disorders or syndromes. Molecular and functional links between syndrom ...
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Journal ArticleNature · May 16, 2013
Postnatal/adult neural stem cells (NSCs) within the rodent subventricular zone (SVZ; also called subependymal zone) generate doublecortin (Dcx)(+) neuroblasts that migrate and integrate into olfactory bulb circuitry. Continuous production of neuroblasts is ...
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Journal ArticleNature · 2013
Postnatal/adult neural stem cells (NSCs) within the rodent subventricular zone (SVZ; also called subependymal zone) generate doublecortin (Dcx) + neuroblasts that migrate and integrate into olfactory bulb circuitry. Continuous production of neuroblasts is ...
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Journal ArticleJ Neurosci · June 27, 2012
Neuropathic pain is a common cause of pain after nerve injury, but its molecular basis is poorly understood. In a post-gene chip microarray effort to identify new target genes contributing to neuropathic pain development, we report here the characterizatio ...
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Journal ArticleMatrix Biol · April 2012
Thrombospondins (TSPs) are a family of large, oligomeric multidomain glycoproteins that participate in a variety of biological functions as part of the extracellular matrix (ECM). Through their associations with a number of binding partners, TSPs mediate c ...
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Journal ArticleProc Natl Acad Sci U S A · August 9, 2011
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Astrocytes regulate synaptic connectivity in the CNS through secreted signals. Here we identified two astrocyte-secreted proteins, hevin and SPARC, as regulators of excitatory synaptogenesis in vitro and in vivo. Hevin induces the formation of synapses bet ...
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Journal ArticleJ Vis Exp · November 16, 2010
One of the most important goals in neuroscience is to understand the molecular cues that instruct early stages of synapse formation. As such it has become imperative to develop objective approaches to quantify changes in synaptic connectivity. Starting fro ...
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Journal ArticleNature · November 11, 2010
The human brain contains more than 100 trillion (10(14)) synaptic connections, which form all of its neural circuits. Neuroscientists have long been interested in how this complex synaptic web is weaved during development and remodelled during learning and ...
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Journal ArticleJ Cell Commun Signal · December 2009
Matricellular proteins, such as thrombospondins (TSPs1-4), SPARC, SPARC-like1 (hevin) and tenascin C are expressed by astrocytes in the central nervous system (CNS) of rodents. The spatial and temporal expression patterns of these proteins suggest that the ...
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Journal ArticleCell · October 16, 2009
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Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein ...
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Journal ArticleCurr Opin Neurobiol · October 2009
Historically, our understanding of synapse formation has been shaped by studies focusing on neurons. However, with advancements in live imaging techniques and molecular and genetic tools we are rapidly uncovering new roles for glia in synapse formation and ...
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Journal Article · December 1, 2008
Long before the discovery of green fluorescent protein (GFP), Ramon y Cajal recognized glia's intimate association with synapses in the brain. Though their function was at that time a mystery, he predicted that glia must be doing more than simply filling t ...
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Journal ArticleJ Cereb Blood Flow Metab · October 2008
Thrombospondins 1 and 2 (TSP-1/2) belong to a family of extracellular glycoproteins with angiostatic and synaptogenic properties. Although TSP-1/2 have been postulated to drive the resolution of postischemic angiogenesis, their role in synaptic and functio ...
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Journal ArticleDev Cell · October 2003
The role of phospholipids in the regulation of membrane trafficking and signaling is largely unknown. Phosphatidylcholine (PC) is a main component of the plasma membrane. Mutants in the Drosophila phosphocholine cytidylyltransferase 1 (CCT1), the rate-limi ...
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Journal ArticleProc Natl Acad Sci U S A · September 2, 2003
Metabotropic glutamate receptors (mGluRs) are responsible for the effects of glutamate in slow synaptic transmission, and are implicated in the regulation of many processes in the CNS. Recently, we have reported the expression and purification of a mGluR f ...
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Journal ArticleProtein Expr Purif · August 2003
Metabotropic glutamate receptors (mGluRs) play important roles in the function and regulation of the central nervous system. Structural studies are necessary for the detailed understanding of their mechanisms of action. However, overexpression and purifica ...
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Journal ArticleEMBO Rep · May 2002
G-protein-coupled receptors (GPCRs) form one of the largest superfamilies of membrane proteins. Obtaining high yields of GPCRs remains one of the major factors limiting a detailed understanding of their structure and function. Photoreceptor cells (PRCs) co ...
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Journal ArticleActa Virol · February 2000
In this study, a 178 amino acids long portion of the hepatitis C virus (HCV) core gene was cloned, sequenced, expressed in Escherichia coli, and purified. The resulting antigen (C178) was tested with human sera enzyme-linked immunosorbent assay (ELISA) in ...
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