Late starting treadmill exercise improves spatial leaning ability through suppressing CREP/BDNF/TrkB signaling pathway following traumatic brain injury in rats
Il-Gyu Ko, Sung-Eun Kim, Lakkyong Hwang, Jun-Jang Jin, Chang-Ju Kim, Bo-Kyun Kim, Hong Kim
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https://www.earticle.net/Article/A331837
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Traumatic brain injury (TBI) causes deficit in spatial learning and mem-ory function. Physical activity ameliorates neurological dysfunction af-ter TBI. We investigated the effect of late starting treadmill exercise on spatial learning ability in relation with cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway using TBI rats. For this study, radial 8-arm maze test, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end label-ing) staining, caspase-3 immunohistochemistry, and western blot for Bax, Bcl-2, BDNF, tyrosine kinase B (TrkB), CREB, and phosphorylated CREP (p-CREB) were performed. TBI was induced by an electromag-netic-controlled cortical impact. The rats in the exercise groups were scheduled to run on a treadmill for 30 min once a day for 8 weeks start-ing 3 weeks after TBI. TBI impaired spatial learning ability and in-creased caspase-3 expression in the hippocampal dentate gyrus. TBI enhanced Bax expression and suppressed Bcl-2 expression in the hip-pocampus. TBI increased BDNF and TrkB expressions, resulted in the enhancement of p-CREB/CREB ratio in the hippocampus. However, treadmill exercise improved spatial learning ability, decreased caspase-3 expression, suppressed Bax expression, and increased Bcl-2 expression. Treadmill exercise alleviated TBI-induced over-expres-sion of BDNF and TrkB, which suppressed phosphorylation of CREB in the hippocampus. In the present study, late starting treadmill exercise improved spatial learning ability through suppressing TBI-induced acti-vation of CREB/BDNF/TrkB signaling pathway after TBI.
목차
Abstract INTRODUCTION MATERIALS AND METHODS Animals and treatments Induction of TBI Exercise protocol Radial 8-arm maze test Tissue preparation Immunohistochemistry for caspase-3Immunohistochemistry was conducted to evaluate Western blotting Data analysis RESULTS Effect of treadmill exercise on the spatial learning ability in the radial 8-arm maze test Effect of treadmill exercise on caspase-3 expression in the hippocampal dentate gyrus Effect of treadmill exercise on Bax and Bcl-2 expressions in the hippocampus Effects of treadmill exercise on BDNF and TrkB expressions in the hippocampus Effects of treadmill exercise on the ratio of p-CREB to CREB in the hippocampus DISCUSSION CONFLICT OF INTEREST ACKNOWLEDGMENTS REFERENCES
Il-Gyu Ko [ Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea, Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea ]
Sung-Eun Kim [ Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea, Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea ]
Lakkyong Hwang [ Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea, Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea ]
Jun-Jang Jin [ Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea, Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea ]
Chang-Ju Kim [ Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea, Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea ]
Bo-Kyun Kim [ Department of Emergency Technology, College of Health Science, Gachon University, Incheon, Korea ]
Hong Kim [ Department of Oriental Sports Medicine, College of Biomedical Science, Daegu Haany University, Gyeongsan, Korea ]
Corresponding author