Abstract
Down-regulated Wnt signaling is involved in brain aging with declined cognitive capacity due to its modulation on neuronal function and synaptic plasticity. However, the molecular mechanisms are still unclear. In the present study, the naturally aged rat model was established by feeding rats from 6 months old to 21 months old. The cognitive capacity of aged rats was compared with young rats as the controls and the aged rats upon 12-week exercise interventions including treadmill running, resistance exercise, and alternating exercise with resistance exercise and treadmill running. Wnt signaling was examined in hippocampal tissues of the rats from different groups. Results indicated that the expression of Dickkopf-1 (DKK-1) as an antagonist of Wnt signal pathway, the activation of GSK-3β, and the hyperphosphorylated Tau were markedly increased as the extension of age. Meanwhile, higher p-β-cateninSer33, 37, Thr41 promoted neuronal degradation of aged rats. In contrast, three kinds of exercise interventions rescued the abnormal expression of DKK-1 and synaptophysin such as PSD-93 and PSD-95 in hippocampal tissues of the aged rats; especially 12-week treadmill running suppressed DKK-1 up-regulation, GSK-3β activation, β-catenin phosphorylation, and hyperphosphorylated Tau. In addition, the down-regulated PI3K/AKT and Wnt signal pathways were observed in aged rats, but could be reversed by resistance exercise and treadmill running. Moreover, the increased Bax and reduced Bcl-2 levels in hippocampal tissues of aged rats were also reversed upon treadmill running intervention. Taken together, down-regulated Wnt signaling suppressed PI3K/Akt signal pathway, aggravated synaptotoxicity, induced neuron apoptosis, and accelerated cognitive impairment of aged rats. However, exercise interventions, especially treadmill running, can attenuate their brain aging process via restoring Wnt signaling and corresponding targets.
Highlights
Aging is the major risk factor for Alzheimer’s disease (AD)
The aging model rats at the age of 21 months old were randomly divided into four groups including natural aging model group (OC), natural aging combined with resistance exercise group (OR), natural aging combined with treadmill training group (OT), and natural aging combined with alternating exercise with resistance exercise and treadmill running group (OM), with 10 rats in each group
Three kinds of exercise interventions can promote the rescuing of cognitive dysfunction partly by restoring Wnt signaling pathway
Summary
Aging is the major risk factor for Alzheimer’s disease (AD). According to the latest report from United Nations, the population over 60 years old in the world is close to 1 billion in 2017. As the increase of life expectancy, population aging will be a serious issue for each country. Neurodegenerative diseases caused by aging are seriously threatening the quality of life of senior people. The number of suffered individuals could rise to more than 100 million by 2050. Exercise Alleviates Brain Aging (Bayod et al, 2015). Current treatments cannot terminate or slow down the progression of AD due to unclear molecular mechanisms involved in AD pathogenesis. Developing an effective strategy to delay aging process and prevent the diseases associated with aging will be an urgent problem
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
