Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, MN 55905, USA.
Neuroscience Program, Rochester, MN 55905, USA.
Cells. 2024 Feb 9;13(4):318. doi: 10.3390/cells13040318.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). Most GABAergic neurons synthesize GABA from glutamate and release it in the synaptic cleft in the CNS. However, astrocytes can also synthesize and release GABA, activating GABA receptors in the neighboring neurons in physiological and pathological conditions. As the primary homeostatic glial cells in the brain, astrocytes play a crucial role in regulating GABA homeostasis and synaptic neurotransmission. Accumulating evidence demonstrates that astrocytic GABA dysregulation is implicated in psychiatric disorders, including alcohol use disorder (AUD) and major depressive disorder (MDD), the most prevalent co-occurring psychiatric disorders. Several current medications and emerging pharmacological agents targeting GABA levels are in clinical trials for treating AUD and MDD. This review offers a concise summary of the role of astrocytic GABA regulation in AUD and MDD. We also provide an overview of the current understanding and areas of debate regarding the mechanisms by which astrocytes regulate GABA in the CNS and their potential significance in the molecular basis of AUD and MDD, paving the way toward future research directions and potential therapeutic target areas within this field.
γ-氨基丁酸(GABA)是中枢神经系统(CNS)中的主要抑制性神经递质。大多数 GABA 能神经元从谷氨酸合成 GABA 并将其释放到 CNS 的突触间隙中。然而,星形胶质细胞也可以合成和释放 GABA,在生理和病理条件下激活邻近神经元的 GABA 受体。作为大脑中的主要稳态神经胶质细胞,星形胶质细胞在调节 GABA 稳态和突触神经传递中起着至关重要的作用。越来越多的证据表明,星形胶质细胞 GABA 失调与精神疾病有关,包括酒精使用障碍(AUD)和重度抑郁症(MDD),这是最常见的共病精神疾病。几种针对 GABA 水平的当前药物和新兴药理学药物正在临床试验中用于治疗 AUD 和 MDD。这篇综述简要总结了星形胶质细胞 GABA 调节在 AUD 和 MDD 中的作用。我们还概述了目前对星形胶质细胞调节 CNS 中 GABA 的机制的理解和争议领域,以及它们在 AUD 和 MDD 的分子基础中的潜在意义,为该领域的未来研究方向和潜在治疗靶点铺平了道路。