Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence

Neuron, Journal Year: 2017, Volume and Issue: 95(3), P. 531 - 549.e9

Published: July 14, 2017

Astrocytes are ubiquitous in the brain and widely held to be largely identical. However, this view has not been fully tested, possibility that astrocytes neural circuit specialized remains unexplored. Here, we used multiple integrated approaches, including RNA sequencing (RNA-seq), mass spectrometry, electrophysiology, immunohistochemistry, serial block-face-scanning electron microscopy, morphological reconstructions, pharmacogenetics, diffusible dye, calcium, glutamate imaging, directly compare adult striatal hippocampal under identical conditions. We found significant differences electrophysiological properties, Ca2+ signaling, morphology, astrocyte-synapse proximity between astrocytes. Unbiased evaluation of actively translated proteomic data confirmed astrocyte diversity circuits. thus report core reveal evidence for within circuits, provide new, database resources approaches explore function throughout brain.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0OGY5MjVkMzgwOGU0NTkwZGMzNTRhMjQwZjZkMWM0OCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc3ODAzMzg0fQ.MwSBbMAp8Z94bVovEvEtEK9rSaCme1FWQaVStp6O8krax6PBRClksqtYhGWrI6xK8ct9tTpHJOavNya9agX01pfBV5Xv2_BxcAlr-eYdkIlnW6ddiNKQ9_7eEHZulgpmyVbQq2DLjKc1qNoV1ABBLI5qYU4yHQPnu-EI2_RASm5h1NErzRmbGIHeglc9V82L8hZBX8NyvUw74JxMPzvU4cgxuX5JBvnXBUOvw2oTkF0oPeBvpSchW6EKQzen4Skxhu-LXb5aAa3LkCMU3JhcCep28BCCVsKkV1kx3RuXhdJgkWD2ucI-70LBWqUvhtG-49ThFs0TB8dIBr74DrFLKA(mp4, (55.46 MB) Download video

Language: Английский

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Function and therapeutic value of astrocytes in neurological diseases

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(5), P. 339 - 358

Published: Feb. 16, 2022

Language: Английский

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Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 251 - 277

Published: Feb. 9, 2021

The immune system of the central nervous (CNS) consists primarily innate cells. These are highly specialized macrophages found either in parenchyma, called microglia, or at CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were thought phagocytes, their function extends well beyond simple removal cell debris during development diseases. Brain-resident cells to be plastic, long-lived, host an outstanding number risk genes for multiple pathologies. As a result, now considered most suitable targets modulating Additionally, recent single-cell technologies enhanced our molecular understanding origins, fates, interactomes, functional statesduring health perturbation. Here, we review current state challenges myeloid biology treatment options related

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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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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Astrocytes: Role and Functions in Brain Pathologies

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: Sept. 27, 2019

Astrocytes are a population of cells with distinctive morphological and functional characteristics that differ within specific areas the brain. Postnatally, astrocytes progenitors migrate to reach their brain area related properties. They have regulatory role functions: implicated in neurogenesis, synaptogenesis, controlling blood-brain barrier permeability maintaining extracellular homeostasis. Mature also express some genes enriched cell progenitors, suggesting they can retain proliferative potential. Considering heterogeneity population, it is not surprising disorders wide range different neuro-pathologies. Brain diseases characterized by active inflammatory state astrocytes, which usually described as up-regulation glial fibrillary acidic protein (GFAP). In particular, loss function result cellular senescence could implications for neurodegenerative disorders, such Alzheimer disease Huntington disease, aging drive induction progression due Ca2+ signals strongly severity/state. Moreover, contribute altered neuronal activity several frontal cortex pathologies ischemic stroke epilepsy. There we describe current knowledge pertaining discuss possibilities target them approach toward pharmacological therapies

Language: Английский

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Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration

Neuropharmacology, Journal Year: 2021, Volume and Issue: 196, P. 108719 - 108719

Published: July 15, 2021

Glutamate is the primary excitatory neurotransmitter of brain. Cellular homeostasis glutamate paramount importance for normal brain function and relies on an intricate metabolic collaboration between neurons astrocytes. extensively recycled astrocytes in a process known as glutamate-glutamine cycle. The recycling closely linked to energy metabolism essential sustain glutamatergic neurotransmission. However, considerable amount also metabolized serves hub connecting glucose amino acid both Disruptions clearance, leading neuronal overstimulation excitotoxicity, have been implicated several neurodegenerative diseases. Furthermore, link gaining attention neurological conditions. In this review, we provide overview dynamics synaptic underlying processes with cellular focus particular, review recently discovered role uptake discuss current advances context Alzheimer's disease Huntington's disease. Understanding regulation glutamate-dependent at synapse will not only increase our insight into mechanisms homeostasis, but may reveal new targets ameliorate neurodegeneration. This article part Neuropharmacology Special Issue 'Glutamate Receptors - Glutamatergic Synapse'.

Language: Английский

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Questions and (some) answers on reactive astrocytes

Glia, Journal Year: 2019, Volume and Issue: 67(12), P. 2221 - 2247

Published: Aug. 19, 2019

Abstract Astrocytes are key cellular partners for neurons in the central nervous system. react to virtually all types of pathological alterations brain homeostasis by significant morphological and molecular changes. This response was classically viewed as stereotypical is called astrogliosis or astrocyte reactivity. It long considered a nonspecific, secondary reaction conditions, offering no clues on disease‐causing mechanisms with little therapeutic value. However, many studies over last 30 years have underlined crucial active roles played astrocytes physiology, ranging from metabolic support, synapse maturation, pruning fine regulation synaptic transmission. prompted researchers explore how these new functions were changed disease, they reported them (sometimes beneficial, mostly deleterious). More recently, cell‐specific transcriptomics revealed that undergo massive changes gene expression when become reactive. observation further stressed reactive may be very different normal, nonreactive could influence disease outcomes. To make picture even more complex, both normal shown molecularly functionally heterogeneous. Very known about specific each subtype play contexts. In this review, we interrogated field identify discuss points consensus controversies astrocytes, starting their name. We then present emerging knowledge cells future challenges field.

Language: Английский

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Cell Type-Specific Transcriptomics Reveals that Mutant Huntingtin Leads to Mitochondrial RNA Release and Neuronal Innate Immune Activation

Neuron, Journal Year: 2020, Volume and Issue: 107(5), P. 891 - 908.e8

Published: July 17, 2020

Language: Английский

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