Details

Autor(en) / Beteiligte

• Liu, Yang
• Guo, Wen
• Hong, Si‐Lu

Titel

Aerobic exercise mitigates hippocampal neuronal apoptosis by regulating DAPK1/CDKN2A/REDD1/FoXO1/FasL signaling pathway in D‐galactose‐induced aging mice

Ist Teil von

• The FASEB journal, 2023-10, Vol.37 (10), p.e23205-n/a

Erscheinungsjahr

2023

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• Brain aging is the most important risk factor for neurodegenerative disorders, and abnormal apoptosis is linked to neuronal dysfunction. Specifically, studies have found that exercise effectively inhibits hippocampal neuronal apoptosis, while the molecular mechanism remains unclear. In the present study, we investigated the impact of aerobic exercise on hippocampal neuronal apoptosis in aging mice and the potential involvement of DAPK1 and its downstream pathways based on recent data that DAPK1 may be associated with neuronal death in neurodegenerative diseases. Senescent mice were subjected to 8 weeks of Aerobic training. Following behavioral testing, hippocampal samples were examined histologically and biochemically to detect pathological changes, neuronal apoptosis, and mRNA and protein levels. We found that the exercise intervention improved spatial memory and alleviated neuronal apoptosis in the brain. Notably, exercise down‐regulated DAPK1 expression and inhibited Fas death receptor transactivation and the mitochondrial apoptotic pathway in the hippocampus. These results shed new light on the protective effect of regular exercise against brain aging though modulating the DAPK1 pathway. Apoptotic cascades are triggered in the hippocampus of mice following D‐galactose induction, which can exacerbate histopathological deterioration and impair cognitive memory. Exercise is an effective approach for slowing the progression of aging, but the mechanism by which exercise inhibits aging‐associated neuronal apoptosis remains unclear. Interestingly, we demonstrated that aerobic exercise downregulated DAPK1 along with its downstream CDKN2A/REDD1/FoXO1 pathway and decreased FoXO1 nuclear transcription, which inhibited the FasL and mitochondria‐mediated apoptotic pathways.