Anti-apoptotic and pro-survival effect of exercise training on early aged hypertensive rat cerebral cortex.

Yi-Jie Liu,Hai-Liang Huang,Shin-Da Lee,Chun-Lei Shan,Ai-Lun Yang,Amadou W Jallow,Zhen-Yang Cui

doi:10.18632/aging.203431

Abstract

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

Highlights

Hypertension (HTN) is considered as the most prevalent and leading cause of most morbidities and mortalities in worldwide health [1]
There were no significant differences in body weight and brain weight among the three groups (WKY, spontaneously early aged hypertensive (SHR), and SHR-EX)
The recorded pulse pressure was higher in SHR group compared with Wistar Kyoto normotensive rats (WKY) and was decreased in SHR-EX compared with SHR group

Summary

Introduction

Hypertension (HTN) is considered as the most prevalent and leading cause of most morbidities and mortalities in worldwide health [1]. Progressive brain damage is one of the adverse complications of hypertension [2]. A previous study revealed that hypertension-induced structural changes in the brain such as vascular remodeling, cerebral microbleeds, cerebral atrophy, and impaired cerebral autoregulation [3]. Some studies reported that chronic hypertension appeared to aggravate Parkinson’s diseases, Alzheimer’s diseases, dementia, and cognitive impairment [4, 5]. Neuroinflammation which was augmented in hypertension was identified as a key determinant resulting in brain dysfunction [7]. High blood pressure deteriorates neuronal functions [9], and causes destruction on both small and large cerebral vessels leading to dementia and brain damage [10]. Strategies to control blood pressure would provide neurological benefits

Methods

Results

Discussion

Conclusion