The Emerging Nature of Astrocyte Diversity

Annual Review of Neuroscience, Journal Year: 2019, Volume and Issue: 42(1), P. 187 - 207

Published: July 8, 2019

Astrocytes are morphologically complex, ubiquitous cells that viewed as a homogeneous population tiling the entire central nervous system (CNS). However, this view has been challenged in last few years with availability of RNA sequencing, immunohistochemistry, electron microscopy, morphological reconstruction, and imaging data. These studies suggest astrocytes represent diverse they display brain area– disease–specific properties functions. In review, we summarize these observations, emphasize areas where clear conclusions can be made, discuss potential unifying themes. We also identify knowledge gaps need to addressed order exploit astrocyte diversity biological phenomenon physiological relevance CNS. thus provide summary perspective on vertebrate

Language: Английский

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Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior

Neuron, Journal Year: 2018, Volume and Issue: 99(6), P. 1170 - 1187.e9

Published: Aug. 30, 2018

Language: Английский

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Molecular basis of astrocyte diversity and morphology across the CNS in health and disease

Science, Journal Year: 2022, Volume and Issue: 378(6619)

Published: Nov. 3, 2022

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, morphology across the mouse central nervous system (CNS). We identified shared region-specific astrocytic genes functions explored cellular origins their regional diversity. gene networks correlated with morphology, several which unexpectedly contained Alzheimer’s disease (AD) risk genes. CRISPR/Cas9–mediated reduction candidate reduced morphological complexity resulted in cognitive deficits. The same were down-regulated human AD, an AD model that displayed other brain disorders. thus provide comprehensive data on diversity mechanisms CNS basis health disease.

Language: Английский

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Astrocyte morphology: Diversity, plasticity, and role in neurological diseases

CNS Neuroscience & Therapeutics, Journal Year: 2019, Volume and Issue: 25(6), P. 665 - 673

Published: March 30, 2019

Summary Astrocytes are the most abundant glial cells in central nervous system (CNS) and participate synaptic, circuit, behavioral functions. The well‐developed protoplasmic astrocytes contain numerous processes forming well‐delineated bushy territories that overlap by as little 5% at their boundaries. This highly complex morphology, with up to approximately 80% of cell's membrane constituted fine dimensions on tens nanometer scale high surface area volume ratios, comes contact synapses, blood vessels, other cells. Recent progress is challenging conventional view morphologically homogeneous throughout brain; instead, they display circuit‐ region‐specific morphological diversity may contribute heterogeneous astrocyte‐neuron spatiotemporal interplay different brain areas. Further, structure found be plastic activity‐dependent. We beginning understand how astrocyte structural plasticity contributes change/loss traditionally known a hallmark for reactive astrogliosis, common pathological feature many neurological disorders. However, recent data suggest deficits preceding astrogliosis drive disease progression. review summarizes advances diversity, plasticity, disease‐related deficits.

Language: Английский

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Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue

Cell, Journal Year: 2019, Volume and Issue: 177(5), P. 1280 - 1292.e20

Published: April 25, 2019

Language: Английский

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Improved tools to study astrocytes

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(3), P. 121 - 138

Published: Feb. 10, 2020

Language: Английский

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A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Feb. 12, 2019

Abstract Adenosine 5′ triphosphate (ATP) is a universal intracellular energy source and an evolutionarily ancient, ubiquitous extracellular signal in diverse species. Here, we report the generation characterization of single-wavelength genetically encoded fluorescent sensors (iATPSnFRs) for imaging cytosolic ATP from insertion circularly permuted superfolder GFP into epsilon subunit F 0 1 -ATPase Bacillus PS3 . On cell surface within cytosol, iATPSnFR 1.0 responds to relevant concentrations (30 μM 3 mM) with fast increases fluorescence. iATPSnFRs can be targeted specific types sub-cellular compartments, imaged standard light microscopes, do not respond other nucleotides nucleosides, when fused red protein function as ratiometric indicators. After careful consideration their modest pH sensitivity, represent promising reagents space cells during variety settings, further application-specific refinements.

Language: Английский

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Behaviorally consequential astrocytic regulation of neural circuits

Neuron, Journal Year: 2020, Volume and Issue: 109(4), P. 576 - 596

Published: Dec. 31, 2020

Language: Английский

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Astrocyte molecular signatures in Huntington’s disease

Science Translational Medicine, Journal Year: 2019, Volume and Issue: 11(514)

Published: Oct. 16, 2019

Astrocyte gene expression is altered in mouse models of Huntington’s disease and postmortem brain samples from patients with HD.

Language: Английский

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Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

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