Cited by 66Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismEpilepsy research and treatment

GABA release from astrocytes in health and disease.

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Kilb, Werner, Kirischuk, Sergei·2022·International Journal of Molecular Sciences

Abstract

Astrocytes are the most abundant glial cells in the central nervous system (CNS) mediating a variety of homeostatic functions, such as spatial K+ buffering or neurotransmitter reuptake. In addition, astrocytes are capable of releasing several biologically active substances, including glutamate and GABA. Astrocyte-mediated GABA release has been a matter of debate because the expression level of the main GABA synthesizing enzyme glutamate decarboxylase is quite low in astrocytes, suggesting that low intracellular GABA concentration ([GABA]i) might be insufficient to support a non-vesicular GABA release. However, recent studies demonstrated that, at least in some regions of the CNS, [GABA]i in astrocytes might reach several millimoles both under physiological and especially pathophysiological conditions, thereby enabling GABA release from astrocytes via GABA-permeable anion channels and/or via GABA transporters operating in reverse mode. In this review, we summarize experimental data supporting both forms of GABA release from astrocytes in health and disease, paying special attention to possible feedback mechanisms that might govern the fine-tuning of astrocytic GABA release and, in turn, the tonic GABAA receptor-mediated inhibition in the CNS.

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Crossref · 10.3390/ijms232415859

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  • Increased astrocytic GABA in Fmr1 KO mice may be physiologically compensatory to maintain homeostasis.

    “Astrocytes can sense extracellular GABA as well as release GABA through ion channels and transporters, controlling its extracellular levels (Kilb and Kirischuk, 2022), suggesting that increased astrocytic GABA in Fmr1 KO mice may be physiologically compensatory to maintain homeostasis.”

    From Astrocytes in fragile X syndrome (2024) · cites this paper as Kilb and Kirischuk, 2022

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Authors
Kilb, W., & Kirischuk, S.
Affiliations
Johannes Gutenberg University Mainz (DE)
Corresponding author
Kirischuk, Sergei
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-12-13
Volume
23
Issue
24
Pages
15859
ISSN
1422-0067 (ISSN-L)
OpenAlex
W4311358637
Cited by
66
References
134
Citations by year
2026: 19 · 2025: 22 · 2024: 15 · 2023: 9 · 2022: 1
FWCI
1.68
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
Keywords
astrocytes, GABA release, GABA transporters, glutamic acid decarboxylase, tonic inhibition, GABAA receptor
MeSH terms
Astrocytes, gamma-Aminobutyric Acid, Neuroglia, Receptors, GABA-A, Glutamic Acid

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