Glia as architects of central nervous system formation and function

Science, Journal Year: 2018, Volume and Issue: 362(6411), P. 181 - 185

Published: Oct. 11, 2018

Glia constitute roughly half of the cells central nervous system (CNS) but were long-considered to be static bystanders its formation and function. Here we provide an overview how diverse dynamic functions glial orchestrate essentially all aspects Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, microglia each influence development, from neuronal birth, migration, axon specification, growth through circuit assembly synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, network-level activity monitoring alteration CNS structure Continued elucidation cell biology, interactions neurons will enrich our understanding formation, health,

Language: Английский

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Astrocyte Crosstalk in CNS Inflammation

Neuron, Journal Year: 2020, Volume and Issue: 108(4), P. 608 - 622

Published: Sept. 7, 2020

Language: Английский

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Identification of region-specific astrocyte subtypes at single cell resolution

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: March 5, 2020

Abstract Astrocytes, a major cell type found throughout the central nervous system, have general roles in modulation of synapse formation and synaptic transmission, blood–brain barrier formation, regulation blood flow, as well metabolic support other brain resident cells. Crucially, emerging evidence shows specific adaptations astrocyte-encoded functions regions, such spinal cord cerebellum. To investigate true extent astrocyte molecular diversity across forebrain we used single-cell RNA sequencing. Our analysis identifies five transcriptomically distinct subtypes adult mouse cortex hippocampus. Validation our data situ reveals spatial positioning defined subtypes, reflecting distribution morphologically physiologically populations. findings are for specialized between within regions. The available through an online database ( https://holt-sc.glialab.org/ ), providing resource on which to base explorations local function brain.

Language: Английский

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Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity

Trends in Immunology, Journal Year: 2020, Volume and Issue: 41(9), P. 758 - 770

Published: Aug. 17, 2020

Astrocytes are neural parenchymal cells that ubiquitously tile the central nervous system (CNS). In addition to playing essential roles in healthy tissue, astrocytes exhibit an evolutionarily ancient response all CNS insults, referred as astrocyte reactivity. Long regarded passive and homogeneous, reactivity is being revealed a heterogeneous functionally powerful component of mammalian innate immunity. Nevertheless, concepts about what comprises it does incomplete sometimes controversial. This review discusses goal differentiating reactive subtypes states based on composite pictures molecular expression, cell morphology, cellular interactions, proliferative state, normal functions, disease-induced dysfunctions. A working model conceptual framework presented for characterizing diversity

Language: Английский

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Modeling Alzheimer’s disease with iPSC-derived brain cells

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 25(1), P. 148 - 167

Published: Aug. 7, 2019

Alzheimer’s disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent models yet failed to benefit human patients. While hope remains that earlier intervention existing will improve outcomes, it becoming increasingly clear new approaches understand and combat the pathophysiology of are needed. Human induced pluripotent stem cell (iPSC) technologies changed face preclinical research iPSC-derived types being utilized study an array conditions, including disease. All major brain can now be differentiated from iPSCs, while complex co-culture systems developed facilitate neuroscience research. Many cellular functions perturbed recapitulated using cells vitro, platforms beginning yield insights into interactions occur between during neurodegeneration. Further, iPSC-based genome editing tools critical understanding roles numerous genes mutations found modify risk past decade. still their relative infancy, these developing hold considerable promise push forward efforts other disorders.

Language: Английский

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Astrocytes and Microglia: In Sickness and in Health

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(3), P. 144 - 154

Published: Feb. 7, 2020

Language: Английский

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Crosstalk Between Astrocytes and Microglia: An Overview

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: July 16, 2020

Based on discoveries enabled by new technologies and analyzed using novel computational tools, neuroscience can be re-conceived in terms of information exchange dense networks intercellular connections rather than the context individual populations, such as glia or neurons.. Cross-talk between neurons microglia astrocytes are has been addressed, however, manner which non-neuronal cells communicate interact remains less well understood. We review this intriguing crosstalk among CNS cells, focusing how it contributes to brain development two neurodegenerative diseases: Alzheimer disease GRN-FTLD most prevalent tumor, astrocytoma. The goal studying these communications is promote our ability combat incurable neurological disorders.

Language: Английский

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Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: March 19, 2020

A plethora of neurological disorders shares a final common deadly pathway known as excitotoxicity. Among these disorders, ischemic injury is prominent cause death and disability worldwide. Brain ischemia stems from cardiac arrest or stroke, both responsible for insufficient blood supply to the brain parenchyma. Glucose oxygen deficiency disrupts oxidative phosphorylation, which results in energy depletion ionic imbalance, followed by cell membrane depolarization, calcium (Ca2+) overload, extracellular accumulation excitatory amino acid glutamate. If tight physiological regulation fails clear surplus this neurotransmitter, subsequent prolonged activation glutamate receptors forms vicious circle between elevated concentrations intracellular Ca2+ ions aberrant release, aggravating effect pathway. The downstream Ca2+-dependent enzymes has catastrophic impact on nervous tissue leading death, accompanied formation free radicals, edema, inflammation. After decades "neuron-centric" approaches, recent research also finally shed some light role glial cells diseases. It becoming more evident that neurons glia depend each other. Neuronal cells, astrocytes, microglia, NG2 glia, oligodendrocytes all have their roles what However, who main contributor pathway, unsuspecting victim? In review article, we summarize so-far-revealed central system, with particular attention ischemia-induced excitotoxicity, its origins, consequences.

Language: Английский

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Neuron-Glia Signaling in Synapse Elimination

Annual Review of Neuroscience, Journal Year: 2019, Volume and Issue: 42(1), P. 107 - 127

Published: July 8, 2019

Maturation of neuronal circuits requires selective elimination synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning these cells, the number, morphology, and function contacts profoundly altered, resulting abnormal connectivity behavioral abnormalities. In addition to their role refinement, have been implicated pathological synapse loss dysfunction following injury or nervous system degeneration adults. regulating glia-mediated still being uncovered, clear complex process involves many cues promote inhibit removal specific Gaining greater understanding signals contribution different cell types will not only provide insight into biological event but be instrumental advancing knowledge brain development neural disease.

Language: Английский

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Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: April 18, 2018

Abstract Non-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- three-dimensional observations revealed in different layers possess distinct morphologies as reflected by differences cell orientation, territorial volume, arborization. The extent ensheathment synaptic clefts layer II/III was greater than those VI. Moreover, gene expression were observed between upper-layer deep-layer Importantly, astrocyte properties abrogated reeler Dab1 conditional knockout mice, which neuronal are disturbed, suggesting prerequisite for This study thus demonstrates existence interactions neurons astrocytes, may underlie their functions.

Language: Английский

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