Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Avenue, 603022 Nizhny Novgorod, Russia.
Federal Research Center Institute of Applied Physics of the Russian Academy of Sciences (IAP RAS), 603950 Nizhny Novgorod, Russia.
Int J Mol Sci. 2023 Jul 31;24(15):12286. doi: 10.3390/ijms241512286.
Astrocytes serve many functions in the brain related to maintaining nerve tissue homeostasis and regulating neuronal function, including synaptic transmission. It is assumed that astrocytes are crucial players in determining the physiological or pathological outcome of the brain aging process and the development of neurodegenerative diseases. Therefore, studies on the peculiarities of astrocyte physiology and interastrocytic signaling during aging are of utmost importance. Calcium waves are one of the main mechanisms of signal transmission between astrocytes, and in the present study we investigated the features of calcium dynamics in primary cultures of murine cortical astrocytes in physiological aging and hypoxia modeling in vitro. Specifically, we focused on the assessment of calcium network dynamics and the restructuring of the functional network architecture in primary astrocytic cultures. Calcium imaging was performed on days 21 ("young" astrocyte group) and 150 ("old" astrocyte group) of cultures' development in vitro. While the number of active cells and frequency of calcium events were decreased, we observed a reduced degree of correlation in calcium dynamics between neighboring cells, which was accompanied by a reduced number of functionally connected cells with fewer and slower signaling events. At the same time, an increase in the mRNA expression of anti-apoptotic factor Bcl-2 and connexin 43 was observed in "old" astrocytic cultures, which can be considered as a compensatory response of cells with a decreased level of intercellular communication. A hypoxic episode aggravates the depression of the connectivity of calcium dynamics of "young" astrocytes rather than that of "old" ones.
星形胶质细胞在大脑中具有多种功能，与维持神经组织内稳态和调节神经元功能有关，包括突触传递。据推测，星形胶质细胞在决定大脑衰老过程和神经退行性疾病发展的生理或病理结果方面起着至关重要的作用。因此，研究衰老过程中星形胶质细胞生理学和细胞间信号传递的特点非常重要。钙波是星形胶质细胞之间信号传递的主要机制之一，在本研究中，我们研究了体外生理衰老和缺氧模拟条件下原代培养的鼠皮质星形胶质细胞中钙动力学的特征。具体而言，我们专注于评估原代星形胶质细胞培养物中钙网络动力学和功能网络结构的重构。在体外培养的第 21 天（“年轻”星形胶质细胞组）和第 150 天（“年老”星形胶质细胞组）进行钙成像。虽然活性细胞的数量和钙事件的频率减少，但我们观察到相邻细胞之间钙动力学的相关性降低，这伴随着功能连接细胞的数量减少，信号事件更少且更慢。与此同时，在“年老”星形胶质细胞培养物中观察到抗凋亡因子 Bcl-2 和连接蛋白 43 的 mRNA 表达增加，这可以被认为是细胞间通讯水平降低的细胞的代偿反应。缺氧发作加剧了“年轻”星形胶质细胞钙动力学连接性的抑制，而不是“年老”星形胶质细胞的抑制。
