Unravelling the Collective Calcium Dynamics of Physiologically Aged Astrocytes under a Hypoxic State In Vitro

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.

Automated summary

This study investigated the characteristics of calcium dynamics in astrocytes in physiological aging and hypoxia modeling. It was found that the number of active cells and frequency of calcium events decreased in old astrocytes. Additionally, the correlation in calcium dynamics between neighboring cells and the number of functionally connected cells decreased. However, the mRNA expression of anti-apoptotic factor Bcl-2 and connexin 43 increased in old astrocytes, indicating a compensatory response.