Effects of physical exercise on serum corticosterone and hippocampal BDNF/proBDNF and neuroinflammation in post-stroke depression in rats

Akira Tani, Harutoshi Sakakima, Nao Nojima, Teruki Matsuoka, Yuta Tachibe, Ryoma Matsuzaki, Yuki Kato, Shogo Kakimoto, Masaki Inadome, Takuya Kawatani, Kazuki Nakanishi
Purpose:

The aim of this study was to examine the effects of physical exercise on serum corticosterone levels, depression-like behavior, and hippocampal pathophysiology using a rat model of PSD. 

Methods:

PSD was induced by microinjection of endothelin-1(ET-1) into the left medial prefrontal cortex and chronic unpredictable mild stress (CUMS). Rats were divided into three groups: PSD, PSD with exercise (Ex), and control (sham). Exercise was conducted by a motorized treadmill for 3 days a week, starting three days after stroke. The therapeutic interventions were lasted for 4 weeks. Serum corticosterone levels, depression-like behavior, and hippocampal pathophysiology, including the expression of brain-derived neurotrophic factor (BDNF), precursor BDNF (proBDNF), doublecortin (DCX), NeuN, and glial cell activation, were examined. 

Results:

Serum corticosterone levels were significantly lower in the Ex-group than those in the PSD group. The expression of BDNF in the CA1 and dentate gyrus was significantly higher in the Ex-groups than in the PSD group. The Ex-group showed a significantly higher hippocampal BDNF/proBDNF ratio than the PSD groups. In addition, the expression of NeuN protein in the Ex-group was significantly higher than the PSD groups. Hippocampal glial cell activation was increased in the PSD group, but decreased in the Ex-groups.  

Conclusion(s):

This study demonstrate that physical exercise treatment ameliorated serum corticosterone levels in PSD. Notably, physical exercise improved BDNF expression, neurogenesis, the BDNF/proBDNF ratio, and neuroinflammation in the hippocampus in PSD. 

Implications:

The present study implicated that rehabilitation such as physical exercise may enhance treatment effects in the patients with PSD. In addition, this study demonstrated that the mechanisms underlying the antidepressant effects of physical exercise on PSD.

Funding acknowledgements:
This work was supported by a grant from the Japan Society for the Promotion of Science, KAKENHI.
Keywords:
post-stroke depression
physical exercise
hippocampal pathophysiology
Primary topic:
Basic science including molecular and cellular health
Second topic:
Neurology: stroke
Third topic:
Neurology
Did this work require ethics approval?:
Yes
Name the institution and ethics committee that approved your work:
This study was approved by the Animal Care Committee of Kagoshima University.
Provide the ethics approval number:
No. M22002
Has any of this material been/due to be published or presented at another national or international conference prior to the World Physiotherapy Congress 2025?:
No

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