Neuroprotective effects of treadmill exercise on BDNF and PI3-K/Akt signaling pathway in the cortex of transgenic mice model of Alzheimer’s disease

Abstract

(AD). Although physical exercise and AD have received attention in the scientific literature, the mechanism through which treadmill exercise may impact the brain insulin signaling of AD has not been elucidated. This study aimed to evaluate the neuroprotective effects of treadmill exercise on apoptotic factors (Bcl-2/Bax ratio, caspase-3), HSP70, COX-2, BDNF and PI3-K/Akt signaling pathway in the cortex of NSE/hPS2m transgenic mice model of AD. Treadmill exercise ameliorated cognitive function in water maze test and significantly increased the level of Bcl-2/Bax ratio and HSP-70 in Tg-exe group compared to Tg-con group; on the other hand, it significantly decreased the expression of caspase-3 and COX-2 in Tg-exe group compared to Tg-con group. In addition, treadmill exercise significantly increased the expression of BDNF and PI3K/Akt in Tg-exe group compared to Tg-con group. Consequently, treadmill exercise improves cognitive function possibly via activating neurotrophic factor, BDNF and PI3k/Akt signaling pathway, and Aβ-induced neuronal cell death in the cortex of Tg mice was markedly suppressed following treadmill exercise. These results suggest that treadmill exercise may be beneficial in preventing or treating Alzheimer’s disease.

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

“…Firstly, mice generally travel greater distances when given access to a running wheel. Typically they run four-five km per day (Clark et al, 2009(Clark et al, , 2008Garrett et al, 2012;Patten et al, 2013;van Praag et al, 1999a) compared to mice on treadmills which typically run 280-700 m per day (Koo et al, 2013;Lin et al, 2015;Yuede et al, 2009;Zhao et al, 2015). Obviously, mice running on treadmills are unable to reach the distances that mice exercising voluntarily on a running wheel can achieve.…”

“…Other studies provide evidence for a curative effect of exercise. Training of 24 month old Tg-NSE/hPS-2 mice on a treadmill for three months was found to reduce hippocampal A␤42 protein and tau phosphorylation as well as improve performance of the mice in the MWM (Koo et al, 2013;Um et al, 2011). A number of other studies also provide evidence for exerciseinduced amelioration of cognitive function in mice in which AD pathology is deemed to be advanced but disappointingly have not included any data on exercise-induced alterations on typical AD pathologies (Marlatt et al, 2013;Rodriguez et al, 2011).…”

Estrogen receptor β deficiency impairs BDNF–5-HT 2A signaling in the hippocampus of female brain: A possible mechanism for menopausal depression

“…mBDNF has been shown to exist in monomeric form with a molecular mass of 14 kDa (Koo et al, 2013; Yan et al, 1997) and trimeric form with a molecular mass of 42 kDa (Dunham et al, 2009; Spires et al, 2004; Wessels et al, 2015). The antibody used in the study detected both of these forms (Fig.…”

PPAR-α agonist regulates amyloid-β generation via inhibiting BACE-1 activity in human neuroblastoma SH-SY5Y cells transfected with APPswe gene

“…PI3-K appears to be an upstream activator of uptake of gene transcription, mRNA translation, and amino acids [26]. Many studies indicate that PI3-K pathway may be associated with AD [26][27][28][29][30].…”