Chronic corticosterone exposure reduces hippocampal astrocyte structural plasticity and induces hippocampal atrophy in mice

• Chronic CORT injection damages the astrocyte structural plasticity.
• Chronic CORT injection reduces hippocampal volume.
• Chronic CORT injection induces depression-like behavior in mice.

Long-term exposure to stress or high glucocorticoid levels significantly reduces hippocampal volume and induces depression-like behavior in rodents; however, the cause of which remains unknown. Increasing evidence shows that astrocytes are the most abundant cells in the central nervous system (CNS). Astrocytes support, nourish, protect, and repair neurons, and these characteristics are closely linked to neuronal activities. This study focused on the effects of corticosterone (CORT) on astrocytes. We probed into the influence of chronic CORT exposure on structural plasticity of astrocytes in hippocampal tissues of male C57BL/6N mice. The number, somal volume, and protrusion length of glial fibrillary acidic protein-positive astrocytes and the hippocampal volume were assayed by immunocytochemistry and quantitative stereological techniques. Results showed that chronic CORT injection induced depression-like behavior in male mice and significantly decreased hippocampal volume, as well as the number of astroctyes, somal volume, and protrusion length in the hippocampus. The reduction in the hippocampal astrocyte structural plasticity may represent the mechanism by which chronic CORT treatment causes hippocampal atrophy and depression-like behavior in male mice.