PDF(Pubmed)
Abstract：
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.
摘要：
γ-氨基丁酸（GABA）是中枢神经系统（CNS）中主要的抑制性神经递质。大多数GABA能神经元从谷氨酸合成GABA并在CNS的突触间隙中释放它。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中的GABA受体。作为大脑中主要的稳态神经胶质细胞，星形胶质细胞在调节GABA稳态和突触神经传递中起关键作用。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），最普遍的共同发生的精神疾病。目前几种针对GABA水平的药物和新兴药物正在临床试验中用于治疗AUD和MDD。这篇综述简要概述了星形胶质细胞GABA调节在AUD和MDD中的作用。我们还提供了关于星形胶质细胞调节CNS中GABA的机制及其在AUD和MDD分子基础中的潜在意义的当前理解和辩论领域的概述。为该领域未来的研究方向和潜在的治疗目标领域铺平道路。
