Background: The contribution of glial cells to the pathophysiology of depression is an emerging research purpose. This study investigated the deficits in glial cells, specifically astrocytes in various brain regions, after the development of depression and then after voluntary running in depressed rats. Materials and methods: Forty-five adult male Wistar rats aged 8–10 weeks were used in the study. A depression model was generated through a forced swimming programme; voluntary running was allowed on rat running wheels; and brain sections were taken from the hippocampus, dentate gyrus (DG), medial prefrontal cortex (mPFC) and cerebellar cortex. After immunostaining with specific antibodies immuno-stain, the astrocytes, oligodendroglia and microglial cells were counted, and certain indices relating astrocytes to other glial cells were calculated. Astrocytic morphology was studied, and the optical density (OD) of glial fibrillary acidic protein (GFAP) immuno-expression was measured in different groups. Results: Compared to the control group, animals in the depression group exhibited significant decreases in the mean astrocyte count in all studied brain areas, significant decreases in GFAP OD values in all areas and significantly reduced values for all glial astrocyte indices in the hippocampus, DG and mPFC. Compared to the rats in the depression group, those in the depression/exercise group exhibited significantly elevated mean astrocyte and oligodendroglia counts in all studied areas, significantly elevated GFAP OD values in all studied areas, and non-significant differences in glial astrocyte indices in the hippocampus, mPFC and cerebellar cortex. Conclusion: Astrocytes, rather than other glia, constitute a basis for the development and/or relief of depression. (Folia Morphol 2020; 79, 3: 419–428)
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