Institute of Molecular Genetics of National Research Centre "Kurchatov Institute", 123182 Moscow, Russia.
Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, 119234 Moscow, Russia.
Int J Mol Sci. 2022 Apr 30;23(9):4999. doi: 10.3390/ijms23094999.
Neurodegenerative diseases and depression are multifactorial disorders with a complex and poorly understood physiopathology. Astrocytes play a key role in the functioning of neurons in norm and pathology. Stress is an important factor for the development of brain disorders. Here, we review data on the effects of stress on astrocyte function and evidence of the involvement of astrocyte dysfunction in depression and Alzheimer's disease (AD). Stressful life events are an important risk factor for depression; meanwhile, depression is an important risk factor for AD. Clinical data indicate atrophic changes in the same areas of the brain, the hippocampus and prefrontal cortex (PFC), in both pathologies. These brain regions play a key role in regulating the stress response and are most vulnerable to the action of glucocorticoids. PFC astrocytes are critically involved in the development of depression. Stress alters astrocyte function and can result in pyroptotic death of not only neurons, but also astrocytes. BDNF-TrkB system not only plays a key role in depression and in normalizing the stress response, but also appears to be an important factor in the functioning of astrocytes. Astrocytes, being a target for stress and glucocorticoids, are a promising target for the treatment of stress-dependent depression and AD.
神经退行性疾病和抑郁症是具有复杂且尚未完全阐明的病理生理学的多因素疾病。星形胶质细胞在神经元的正常和病理功能中起着关键作用。应激是导致脑疾病发展的重要因素。在这里，我们回顾了应激对星形胶质细胞功能的影响的数据，并提供了星形胶质细胞功能障碍与抑郁症和阿尔茨海默病（AD）之间关系的证据。生活应激事件是抑郁症的一个重要危险因素；与此同时，抑郁症也是 AD 的一个重要危险因素。临床数据表明，在这两种病理中，大脑的同一区域——海马体和前额叶皮层（PFC）都发生了萎缩性变化。这些大脑区域在调节应激反应中起着关键作用，并且最容易受到糖皮质激素的作用。PFC 星形胶质细胞在抑郁症的发展中起着关键作用。应激改变星形胶质细胞的功能，不仅会导致神经元，而且还会导致星形胶质细胞发生细胞焦亡性死亡。BDNF-TrkB 系统不仅在抑郁症和正常化应激反应中起着关键作用，而且似乎也是星形胶质细胞功能的一个重要因素。星形胶质细胞是应激和糖皮质激素的靶点，因此是治疗应激相关性抑郁症和 AD 的有希望的靶点。
