Aging and voluntary exercise's effects on Aβ1-42 levels, endoplasmic reticulum stress factors, and apoptosis in the hippocampus of old male rats.

Within the aging cortex, amyloid beta peptide (Aβ) is a crucial element of the senile plaques, a hallmark feature often observed in cases of Alzheimer's disease (AD). The UPR (unfolded protein response), a cellular mechanism for protein folding, is switched on by Aβ accumulation. Endoplasmic reticulum (ER) stress has been identified as playing a role in aging and the development of neurodegenerative diseases. The exact molecular pathways leading to perishing of cells from Aβ-induced ER stress, as well as the impact of voluntary exercise on these mechanisms, are still subjects awaiting a definitive answer yet. In the current study, 18 male Wistar rats were included: 6 young rats (3 months old; 200-250 g) in the Young Control group, and 12 old rats (18 months old; 400-430 g) randomly allocated to the Old Control and Old Exercise groups. The rat cages had running wheels for them to voluntarily run on for 8 weeks. This was followed by Western blotting, immunohistochemical staining, biochemical as well as morphological analyses. Voluntary exercise reduced Aβ1-42 deposition (P < 0.001) and inhibited the activation of caspase-8 (P < 0.001) and caspase-12 (P < 0.01), and on top of that down-regulated the expression of ATF6 (P < 0.001), CHOP (P < 0.01), and p-PERK (P < 0.05) proteins in the hippocampus of old male rats. Exercise amplified the population of Bcl-2-expressing cells and decreased the population of Bax-expressing cells in the hippocampus of the Old Exercise group (P < 0.001). Voluntary exercise inhibited the apoptotic pathways and suppressed the activation of UPR signaling pathways. Hence, voluntary exercise may be a therapeutic strategy and a promising approach to prevent AD through modulation of Aβ-induced ER stress.