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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Astrocyte morphology

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(7), P. 547 - 565

Published: Oct. 26, 2023

Astrocytes are predominant glial cells that tile the central nervous system (CNS). A cardinal feature of astrocytes is their complex and visually enchanting morphology, referred to as bushy, spongy, star-like. precept this review such morphological shapes evolved allow contact signal with diverse at a range distances in order sample, regulate, contribute extracellular milieu, thus participate widely cell–cell signaling during physiology disease. The recent use improved imaging methods cell-specific molecular evaluations has revealed new information on structural organization underpinnings astrocyte mechanisms morphogenesis, contributions disease states reduced morphology. These insights have reignited interest complexity cornerstone fundamental biology critical substrate for multicellular spatial physiological interactions CNS.

Language: Английский

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A conceptual framework for astrocyte function

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(11), P. 1848 - 1856

Published: Oct. 19, 2023

Language: Английский

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Astrocyte heterogeneity and interactions with local neural circuits

Essays in Biochemistry, Journal Year: 2023, Volume and Issue: 67(1), P. 93 - 106

Published: Feb. 7, 2023

Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into neuropil, where they interact with a variety of other cell types, including neurons at synapses. now known to be active players in all aspects synaptic life cycle, synapse formation and elimination, maturation, maintenance homeostasis modulation transmission. Traditionally, astrocytes have been studied as homogeneous group cells. However, recent studies uncovered surprising degree heterogeneity their development function, suggesting that may matched support local circuits. Hence, better understanding astrocyte its implications needed understand brain function.

Language: Английский

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Astrocytes in selective vulnerability to neurodegenerative disease

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(4), P. 289 - 302

Published: March 22, 2024

Selective vulnerability of specific brain regions and cell populations is a hallmark neurodegenerative disorders. Mechanisms selective involve neuronal heterogeneity, functional specializations, differential sensitivities to stressors pathogenic factors. In this review we discuss the growing body literature suggesting that, like neurons, astrocytes are heterogeneous specialized, respond integrate diverse inputs, induce effects on function. disease, undergo specific, context-dependent changes that promote different trajectories outcomes. We propose contribute through maladaptive transitions context-divergent phenotypes impair functions. Further studies multifaceted roles in disease may provide new therapeutic approaches enhance resilience against

Language: Английский

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Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice

Neuron, Journal Year: 2024, Volume and Issue: 112(20), P. 3412 - 3423.e6

Published: Aug. 19, 2024

Astrocytes are morphologically complex cells that serve essential roles. They widely implicated in central nervous system (CNS) disorders, with changes astrocyte morphology and gene expression accompanying disease. In the Sapap3 knockout (KO) mouse model of compulsive anxiety-related behaviors related to obsessive-compulsive disorder (OCD), striatal astrocytes display reduced altered actin cytoskeleton Gi-G-protein-coupled receptor (Gi-GPCR) signaling proteins. Here, we show normalizing morphology, cytoskeleton, homeostatic support functions by targeting Gi-GPCR pathway using chemogenetics corrected phenotypes KO mice, including behaviors. Our data portend an astrocytic pharmacological strategy for rescuing brain disorders include compromised tissue support.

Language: Английский

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Astrocyte Calcium Signaling

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(10), P. a041353 - a041353

Published: May 20, 2024

Misha B. Ahrens1, Baljit S. Khakh2 and Kira E. Poskanzer3 1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA 2Department of Physiology Department Neurobiology, University California Los Angeles, 90095, 3Department Biochemistry & Biophysics, California, San Francisco, 94143, Correspondence: ahrensm{at}janelia.hhmi.org; bkhakh{at}mednet.ucla.edu; kira.poskanzer{at}ucsf.edu

Language: Английский

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Astrocyte structural heterogeneity in the mouse hippocampus

Glia, Journal Year: 2023, Volume and Issue: 71(7), P. 1667 - 1682

Published: March 22, 2023

Abstract Astrocytes are integral components of brain circuits, where they sense, process, and respond to surrounding activity, maintaining homeostasis regulating synaptic transmission, the sum which results in behavior modulation. These interactions possible due their complex morphology, composed a tree‐like structure processes cover defined territories ramifying mesh‐like system fine leaflets unresolved by conventional optic microscopy. While recent reports devoted more attention dynamic with synapses, our knowledge about “backbone” physiological conditions is incomplete. Recent transcriptomic studies described astrocyte molecular diversity, suggesting structural heterogeneity regions such as hippocampus, crucial for cognitive emotional behaviors. In this study, we carried out analysis astrocytes across hippocampal subfields Cornu Ammonis area 1 (CA1) dentate gyrus dorsoventral axis. We found that display subfields, conserved along further appear contribute an exocytosis‐dependent manner signaling loop maintains backbone structure. findings reveal appears follow layer‐specific cues depend on neuro‐glial environment.

Language: Английский

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Dissociation Between Neuronal and Astrocytic Calcium Activity in Response to Locomotion in Mice

Function, Journal Year: 2023, Volume and Issue: 4(4)

Published: Jan. 1, 2023

Abstract Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we performed calcium (Ca2+) imaging these two cell types somatosensory cortex head-fixed mice moving on airlifted platform. Ca2+ activity significantly increased during locomotion from low quiescence level. signals first appeared distal processes then propagated to astrocytic somata, where it became larger exhibited oscillatory behaviour. Thus, soma operates as integrator amplifier signal. In neurons, was pronounced quiescent periods further locomotion. Neuronal concentration ([Ca2+]i) rose almost immediately following onset locomotion, whereas lagged by several seconds. Such long lag suggests that [Ca2+]i elevations are unlikely be triggered synapses among local neurons. responses pairs consecutive episodes did not differ while were diminished second astrocytes. refractoriness may arise distinct mechanisms underlying signal generation. bulk enters through channels plasma membrane allowing for steady-level repetitive runs. Astrocytic originate intracellular stores, depletion which affects subsequent signals. Functionally, neuronal reflects sensory input processed dynamics is likely provide metabolic homeostatic support within brain active milieu.

Language: Английский

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Control of Ca²⁺ signals by astrocyte nanoscale morphology at tripartite synapses

Glia, Journal Year: 2022, Volume and Issue: 70(12), P. 2378 - 2391

Published: Sept. 13, 2022

Much of the Ca

Language: Английский

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