The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

Abstract

Abstract. Exercise training was suggested as a practical therapeutic strategy for human subjects suffering from Alzheimer's disease (AD) in our previous study. Therefore, the purpose of this study was to investigate the effects of combining exercise training with the administration of antioxidants on the pathological phenotype of AD. To accomplish this, non-transgenic mice (Non-Tg) and NSE/ APPsw Tg mice were treated with ·-lipoic acid and treadmill exercised for 16 weeks, after which their brains were evaluated to determine whether any changes in the pathological phenotype-related factors occurred. The results indicated that (i) the combination-applied (COMA) Tg group with exercise training (ET) and ·-lipoic acid administration (LA) showed ameliorated spatial learning and memory compared to the sedentary (SED)-Tg and single-treatment groups; (ii) there were no differences in the level of Aß-42 peptides across groups; (iii) the level of glucose transporter-1 and brain-derived neurotrophic factor proteins were highly increased in the COMA group, (iv) ET and LA did not induce a synergistic effect on the expression of heat shock protein-70 and apoptotic proteins including Bax and caspase-3; (v) the levels of SOD-1 and CAT suppressing oxidative stress were extensively higher in the COMA than in the singletreated groups and (vi) there were no significant differences across groups regarding these serum characteristics, although these levels were lower than the SED-Tg group. Taken together, these results suggest that the combination with ET and LA may contribute to protect the neuron injury induced by Aß peptides and may be considered an effective therapeutic strategy for human subjects suffering from AD.

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

“…[52] suggested that neuroprotective by Akt may be regulated through downstream factor of HSP-70 expression, indicating that deficiency of HSP70 is possibly caused by the Aβ-induced down-regulation of Akt protein. The present study showed that the level of HSP70 was decreased in the cortex of Tg mice compared to non Tg mice; however, treadmill exercise could increase HSP70 protein which is in accordance with previous study [27,37,38]. Therefore, these results demonstrated that the activation of PI3-K/Akt signaling and HSP70 might ameliorate the cognitive dysfunction in the cortex of AD.…”

“…In addition, caspase-3, a pro-apoptosis factor, is activated during the last step of apoptosis and could be decreased by the Bcl-2 and increased by the Bax protein [36]. We found that the level of caspase-3 proteins were increased in the cortex of Tg mice compared to non-Tg mice while treadmill exercise induced down-regulation of the caspase-3 in the cortex of Tg mice, which was consistent with previous reports [27,37,38]. Furthermore, cyclooxygenase-2 (COX-2) contributes to synaptic plasticity and memory function whereas when overexpressed it has been associate with neurotoxicity in AD [39].…”

The role of inflammatory processes in Alzheimer’s disease

“…Disappointingly, there is no evidence that NSAIDs have any effect in changing disease progression, and their use may actually be detrimental (Willard et al 2000;Moore and O'Banion 2002;Martin et al 2008;Wolfson et al 2002). Several compounds with anti-oxidative properties, such as vitamin E, alpha lipoic acid and resveratrol are also being investigated for effectiveness in slowing the progression of AD, but there has been no conclusive evidence of benefit (Granzotto and Zatta 2011;Isaac et al 2008;Cho et al 2010).…”

Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers

“…Neuroscience 301 (2015) [480][481][482][483][484][485][486][487][488][489][490][491][492][493][494][495] expression/activation of several pro-apoptotic proteins (Cho et al, 2010;Um et al, 2011) and increased mitochondrial biogenesis (Steiner et al, 2011) and antioxidant capacity (Camiletti-Moiron et al, 2013). However, other still unknown mitochondrial-mediated mechanisms may also be involved, contributing to the improved functional phenotype associated with exercise.…”