Diversity of astrocyte functions and phenotypes in neural circuits

Khakh, Baljit S; Sofroniew, Michael V

doi:10.1038/nn.4043

Cited by 1,239Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsNeurogenesis and neuroplasticity mechanisms

Diversity of astrocyte functions and phenotypes in neural circuits

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Khakh, Baljit S, Sofroniew, Michael V·2015·Nature Neuroscience

DOI 10.1038/nn.4043PMC PMC5258184

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Abstract

Astrocytes tile the entire CNS. They are vital for neural circuit function, but have traditionally been viewed as simple, homogenous cells that serve the same essential supportive roles everywhere. Here, we summarize breakthroughs that instead indicate that astrocytes represent a population of complex and functionally diverse cells. Physiological diversity of astrocytes is apparent between different brain circuits and microcircuits, and individual astrocytes display diverse signaling in subcellular compartments. With respect to injury and disease, astrocytes undergo diverse phenotypic changes that may be protective or causative with regard to pathology in a context-dependent manner. These new insights herald the concept that astrocytes represent a diverse population of genetically tractable cells that mediate neural circuit-specific roles in health and disease.

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Vimentin and GFAP link astrocyte structure and gliovascular function, and are associated with cytoplasmic proteins participating in signal transduction pathways.
“Vimentin and GFAP link astrocyte structure and gliovascular function [90, 92], and are associated with cytoplasmic proteins [92] participating in signal transduction pathways [44, 45, 106, 107].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp>APOE3</scp> Christchurch homozygote glioprotection (2023) · cites this paper as [107]
The 'Morphological complexity' section says GFAP is found in astrocytes’ major branches, supporting a limited link between GFAP and astrocyte structure. Our copy does not mention vimentin or establish that GFAP and vimentin link structure to gliovascular function or are associated with cytoplasmic proteins. The signal-transduction clause is attached to other citations, so it is not assessed against this source. (LLM, conf=0.80)
Experimental — accuracy not yet measured
Astrocyte reactivity is tightly linked to endothelial, which are in turn associated with loss of vascular structural integrity and opening of the BBB.
“Astrocyte reactivity is tightly linked to endothelial [50], which are in turn associated with loss of vascular structural integrity and opening of the BBB [15, 28, 38, 45, 107, 109, 121].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp>APOE3</scp> Christchurch homozygote glioprotection (2023) · cites this paper as [107]
The citation [50] is attached to the asserted link between astrocyte reactivity and endothelial cells, not to the later BBB claim. The section “Two functionally distinct categories of reactive astrocytes” describes proliferation of perivascular astrocytes after injury, but does not establish a tight link between astrocyte reactivity and endothelial cells. Searches for endothelial involvement and vascular integrity found no passage addressing that link; page numbers were unavailable in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Astrocytes regulate synapse number and synaptic communication and support neuronal health and homeostasis in the developing and adult brain.
“In the developing and adult brain, non-neuronal glial cells, in particular astrocytes, carry out important functions that regulate synapse number and synaptic communication and support neuronal health and homeostasis (Khakh and Sofroniew, 2015).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Khakh and Sofroniew, 2015
In the adult brain, astrocytes maintain neuronal and synaptic function in part through thousands of fine processes that ensheath neuronal synapses.
“In the adult brain, astrocytes maintain neuronal and synaptic function, in part through thousands of fine processes that ensheath neuronal synapses (Khakh and Sofroniew, 2015).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Khakh and Sofroniew, 2015

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Transgenic mice expressing a cameleon fluorescent Ca2+ indicator in astrocytes and Schwann cells allow study of glial cell Ca2+ signals in situ and in vivo
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Authors: Khakh, B. S., & Sofroniew, M. V.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Khakh, Baljit S
Sofroniew, Michael V
ORCID: Khakh, Baljit S
Sofroniew, Michael V
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2015-06-25
Volume: 18
Issue: 7
Pages: 942-952
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.4043
PMC: PMC5258184
OpenAlex: W1594747697
Cited by: 1,239
References: 147
Citations by year: 2026: 101 · 2025: 125 · 2024: 110 · 2023: 132 · 2022: 134 · 2021: 165 · 2020: 126 · 2019: 106 · 2018: 99 · 2017: 69 · 2016: 61 · 2015: 9
FWCI: 9.57
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute of Mental Health (R01MH099559, MH104069, MH099559A, DP1MH104069)
National Institute on Drug Abuse (R01DA016602, DA016602)
National Institute of Neurological Disorders and Stroke (NS084030, NS060677, R01NS060677, R01NS057624, R01NS084030)
National Center for Research Resources (RR 04050, P41RR004050, RR RR08605, P41RR008605)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: astrocytes, astrocyte heterogeneity, astrocyte phenotype, neural circuits, subcellular signaling, astrocyte activation, CNS dysfunction
MeSH terms: Animals, Astrocytes, Central Nervous System Diseases, Phenotype, Signal Transduction

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Diversity of astrocyte functions and phenotypes in neural circuits

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