The positive effects of running exercise on hippocampal astrocytes in a rat model of depression

Abstract

Running exercise has been shown to alleviate depressive symptoms, but the mechanism of its antidepressant effect is still unclear. Astrocytes are the predominant cell type in the brain and perform key functions vital to central nervous system (CNS) physiology. Mounting evidence suggests that changes in astrocyte number in the hippocampus are closely associated with depression. However, the effects of running exercise on astrocytes in the hippocampus of depression have not been investigated. Here, adult male rats were subjected to chronic unpredictable stress (CUS) for 5 weeks followed by treadmill running for 6 weeks. The sucrose preference test (SPT) was used to assess anhedonia of rats. Then, immunohistochemistry and modern stereological methods were used to precisely quantify the total number of glial fibrillary acidic protein (GFAP)+ astrocytes in each hippocampal subregion, and immunofluorescence was used to quantify the density of bromodeoxyuridine (BrdU)+ and GFAP+ cells in each hippocampal subregion. We found that running exercise alleviated CUS-induced deficit in sucrose preference and hippocampal volume decline, and that CUS intervention significantly reduced the number of GFAP+ cells and the density of BrdU+/GFAP+ cells in the hippocampal CA1 region and dentate gyrus (DG), while 6 weeks of running exercise reversed these decreases. These results further confirmed that running exercise alleviates depressive symptoms and protects hippocampal astrocytes in depressed rats. These findings suggested that the positive effects of running exercise on astrocytes and the generation of new astrocytes in the hippocampus might be important structural bases for the antidepressant effects of running exercise.

Ginkgo Biloba Extract Reduces Cardiac and Brain Inflammation in Rats Fed a HFD and Exposed to Chronic Mental Stress through NF-κB Inhibition

“…The hippocampus is divided into CA1, CA2, CA3, and dentate gyrus (DG). The CA1 has been reported to be linked with depression [ 23 ]. Accordingly, we chose to focus on the CA1 in this study.…”

Neuroprotective Effects of Physical Activity via the Adaptation of Astrocytes

“…In contrast, it has been shown that moderate treadmill exercise (20 min/day) for 4 weeks decreased the GFAP content in the rat hippocampus [105]. Recently, the study demonstrated that 6 weeks of running exercise significantly increased the number of GFAP+ cells and the density of BrdU+/GFAP+ cells in the hippocampal CA1 region and DG in a rat model of depression, suggesting the role of exercise to promote the generation of new astrocytes [106]. Interestingly, high levels of cleaved caspase-3 positive astrocytes were found in hippocampal CA1 and DG regions after an acute bout of exercise [107].…”

Glia-Driven Brain Circuit Refinement Is Altered by Early-Life Adversity: Behavioral Outcomes

“…Further, voluntary wheel running has been shown to rescue alterations to microglia number and function in the adult cerebellum in a rodent model of Fetal Alcohol Spectrum Disorders (Gursky et al, 2020 ) and is predicted to support myelination in the adolescent brain of children with a history of prenatal alcohol exposure (Tomlinson et al, 2016 ; Wozniak et al, 2019 ). Exercise increases astrocytic coverage of blood vessels (Leardini-Tristaõ et al, 2020 ) and upregulates the number of GFAP-positive astrocytes in the HPC following ELA exposure (Belaya et al, 2020 ; Li et al, 2021 ). These astrocytic changes prevent neurodegeneration (Leardini-Tristaõ et al, 2020 ), cognitive impairment associated with Alzheimer’s disease (Belaya et al, 2020 ), depression, and lowered HPC volume (Li et al, 2021 ).…”

“…Exercise increases astrocytic coverage of blood vessels (Leardini-Tristaõ et al, 2020 ) and upregulates the number of GFAP-positive astrocytes in the HPC following ELA exposure (Belaya et al, 2020 ; Li et al, 2021 ). These astrocytic changes prevent neurodegeneration (Leardini-Tristaõ et al, 2020 ), cognitive impairment associated with Alzheimer’s disease (Belaya et al, 2020 ), depression, and lowered HPC volume (Li et al, 2021 ). Microglial activation and population in HPC are reduced following exercise (Kohman et al, 2013 ; Mee-inta et al, 2019 ).…”