Figure 1 (IMAGE)
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Once thought to be merely supporting cells in the brain, astrocytes now seem to be the most appropriate cells to regulate γ-aminobutyric acid (GABA) tone. Astrocytes have a positional advantage over other cell types because, as part of the tripartite synapse, they are located close to the extrasynaptic sites that largely regulate the induction of tonic GABA current in neurons. Moreover, astrocytes are distinct from other brain cells because they have at least one mechanism for synthesizing, releasing, and clearing GABA, and molecular studies have demonstrated that they, rather than neurons, regulate GABA tone in different brain regions. For example, cerebellar astrocytes use monoamine oxidase B (MAO-B) to synthesize GABA, and thalamic astrocytes use diamine oxidase (DAO) to synthesize GABA. Cerebellar, thalamic, hippocampal, and dorsal root ganglia astrocytes release GABA through BEST1, and ventral tegmental area (VTA) astrocytes release GABA through LRRC8A. That astrocytes have all three GABA regulatory mechanisms underscores their enormous role in regulating GABA tone. In other words, it suggests that changes in astrocytes (such as increased GABA synthesis, increased GABA release, or decreased GABA clearance) can directly lead to changes in GABA tone and modulate cognitive function. GABA-T, GABA transaminase; GAD, glutamate decarboxylase; GAT, GABA transporter; SSADH, succinic semialdehyde dehydrogenase; TCA, tricarboxylic acid.
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