Effects of Aerobic Exercise on Tau and Related Proteins in Rats with Photochemically-Induced Infarction

Article type: Research Article

Authors: Joa, Kyung-Lim^a | Mankhong, Sakulrat^{b; c} | Kim, Sujin^{b; c} | Moon, Sohee^{b; c} | Lee, Kyoung-Hee^d | Yoo, Young-Hwan^a | Hwang, Byeong-Hun^e | Baek, Jong-Won^e | Kang, Ju-Hee^{b; c; *}

Affiliations: [a] Department of Physical & Rehabilitation Medicine, College of Medicine, Inha University, Incheon, Republic of Korea | [b] Department of Pharmacology, College of Medicine, Inha University, Incheon, Republic of Korea | [c] Hypoxia-Related Diseases Research Center, College of Medicine, Inha University, Incheon, Republic of Korea | [d] Department of Occupational Therapy, Baekseok University, Chungnam, Republic of Korea | [e] Industry-Academia Cooperation Group, Baekseok University, Chungnam, Republic of Korea

Correspondence: [*] Correspondence to: Dr. Ju-Hee Kang, Department of Pharmacology, Hypoxia-related Diseases Research Center, College of Medicine, Inha University, Room 1015, 60th Anniversary Hall, 100, Inha-ro, Nam-gu, Incheon 22212, Republic of Korea. Tel.: +82 32 860 9872; Fax: +82 32 887 7488; E-mail: johykang@inha.ac.kr.

Abstract: Background:Recent evidence indicates brain ischemia is associated with accumulations of abnormal tau and related proteins. However, the effects of aerobic training on these proteins have not been evaluated. Objective:We aimed to evaluate the effect of aerobic exercise on the phosphorylation and acetylation of tau and on the expressions of tau related proteins in a rat stroke model and to compare the effects of aerobic exercise with those observed in our previous study on task specific training (TST). Methods:Twenty-four Sprague– Dawley rats with photothrombotic cortical infarction were used in the current study. The rehabilitation group (RG) received treadmill training 40 min/day for 28 days, whereas the sedentary group (SG) did not receive any type of training. Functional tests such as the single pellet reaching task, rotarod, and radial arm maze tests were performed weekly for 4 weeks post-infarction. Results:Levels of p-taus396 and p-AMPK were found to be lower in ipsilateral cortices in the RG than in the SG (p < 0.05). Levels of p-taus262, Ac-tau, p-GSK3βS9, p-Akt, p-Sin1, and p-P70-S6K were significantly lower in ipsilateral than in contralateral cortices in the RG (p < 0.05). Aerobic training also improved motor, balance, and memory functions. Conclusion:Aerobic training inhibited the phosphorylation and acetylation of tau and modulated the expressions of tau related proteins after stroke by modifying the p70-S6K pathway and p-AMPK. By comparison with our previous study on the effects of TST, we have evidence to suggest that TST and aerobic exercise differ, although both types of rehabilitation inhibit tau phosphorylation and acetylation.

Keywords: Aerobic training, dementia, phosphorylated tau, rehabilitation, stroke, tau

DOI: 10.3233/JAD-200250

Journal: Journal of Alzheimer's Disease, vol. 76, no. 4, pp. 1391-1402, 2020