GABA release from astrocytes in health and disease.
Open accessAbstract
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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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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Astrocyte metabolism and signaling pathways in the CNS
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“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.”
BackgroundGABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders
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Aranda, H., Jones, N., Haroon, H., & Choi, D. (2026) · Addiction Biology · doi:10.1111/adb.70195
- 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)
- PMC
- PMC9784789
- 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
- gold
- doi.org
- Licence
- 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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