Park Beomjo, Choi Gee Euhn
College of Veterinary Medicine, Jeju National University, Jeju 63243, South Korea.
Laboratory of Veterinary Biochemistry, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju 63243, South Korea; Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, South Korea.
Prog Neurobiol. 2025 Aug;251:102786. doi: 10.1016/j.pneurobio.2025.102786. Epub 2025 Jun 6.
Major depressive disorder (MDD) is a prevalent psychiatric condition that affects millions of people worldwide and is a leading cause of disability. Chronic stress is a key factor in the development of MDD, leading to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated glucocorticoid levels, which in turn affect brain function and structure. Astrocytes, crucial for maintaining central nervous system (CNS) homeostasis, play a significant role in the pathophysiology of MDD. Dysregulation of glucocorticoid signaling in astrocytes contributes to changes in astrocyte survival, reactivity, metabolism, neurotrophic support, gliotransmitter release, and neuroinflammation, exacerbating depressive symptoms. This review explains the necessity for exploring the effects of glucocorticoid on astrocytes and subsequent MDD progression. Firstly, we briefly explore the glucocorticoid signaling and the multifaceted function of astrocytes. Then, this study discusses the mechanisms by which chronic stress and glucocorticoid exposure induce astrocyte-mediated neurodegenerative changes, highlighting the importance of targeting glucocorticoid-related signaling of astrocytes in developing therapeutic interventions for MDD. Understanding these mechanisms could lead to the development of more effective treatments aimed at restoring astrocyte function and alleviating MDD.
重度抑郁症（MDD）是一种普遍存在的精神疾病，影响着全球数百万人，是导致残疾的主要原因。慢性应激是MDD发病的关键因素，会导致下丘脑-垂体-肾上腺（HPA）轴过度激活和糖皮质激素水平升高，进而影响脑功能和结构。星形胶质细胞对维持中枢神经系统（CNS）的稳态至关重要，在MDD的病理生理学中发挥着重要作用。星形胶质细胞中糖皮质激素信号的失调会导致星形胶质细胞存活、反应性、代谢、神经营养支持、神经递质释放和神经炎症的变化，加剧抑郁症状。这篇综述解释了探索糖皮质激素对星形胶质细胞的影响以及随后MDD进展的必要性。首先，我们简要探讨糖皮质激素信号和星形胶质细胞的多方面功能。然后，本研究讨论了慢性应激和糖皮质激素暴露诱导星形胶质细胞介导的神经退行性变化的机制，强调了在开发MDD治疗干预措施时靶向星形胶质细胞糖皮质激素相关信号的重要性。了解这些机制可能会导致开发出更有效的治疗方法，旨在恢复星形胶质细胞功能并缓解MDD。
