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J Exerc Rehabil. 2018 Jun 30;14(3):327-334. doi: 10.12965/jer.1836248.124. eCollection 2018 Jun.

Late starting treadmill exercise improves spatial leaning ability through suppressing CREP/BDNF/TrkB signaling pathway following traumatic brain injury in rats.

Ko IG1,2, Kim SE1,2, Hwang L1,2, Jin JJ1,2, Kim CJ1,2, Kim BK3, Kim H4.

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Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea.
Department of Emergency Technology, College of Health Science, Gachon University, Incheon, Korea.
Department of Oriental Sports Medicine, College of Biomedical Science, Daegu Haany University, Gyeongsan, Korea.


Traumatic brain injury (TBI) causes deficit in spatial learning and memory function. Physical activity ameliorates neurological dysfunction after 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 labeling) 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 electromagnetic-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 starting 3 weeks after TBI. TBI impaired spatial learning ability and increased 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-expression 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 activation of CREB/BDNF/TrkB signaling pathway after TBI.


Apoptosis; Brain-derived neurotrophic factor; Spatial learning ability; Traumatic brain injury; Treadmill exercise; cAMP-response element binding protein

Conflict of interest statement

CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.

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