In:
Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 4 ( 2022-4), p. 551-565
Abstract:
The molecular mechanisms by which physical exercise produces beneficial effects on pathologic features and behavioral symptoms of Alzheimer’s disease (AD) are not well understood. Herein, we examined whether regular moderate exercise could improve cognitive function and produce transcriptomic responses in the brain. Methods Four groups of mice were studied: nontransgenic control, mice expressing the human presenilin-2 wild type, mice expressing the human presenilin-2 with the N141I mutation (Tg-PS2m), and Tg-PS2m that were subjected to treadmill exercise (TE) at a speed of 10 m·min −1 for 50 min·d −1 , 5 d·wk −1 , for 6 wk (Tg-PS2m/Ex). Results Tg-PS2m/Ex mice exhibited increased preference in exploring a novel object than Tg-PS2m in the novel object recognition test, whereas differences observed in the water maze test and passive avoidance test were not significant. Western blot and histological analyses using amyloid oligomer (A11) and β-amyloid (6E10) antibody indicated that amyloid oligomer-reactive bands and plaque deposition in the hippocampus were reduced, although not significantly, after TE. Transcriptomic (RNA-sequencing) analysis and subsequent protein analysis revealed that the cell cycle regulatory gene, Cdc28 protein kinase regulatory subunit 2 ( Cks2 ), was decreased, and the cell cycle– and apoptotic cell death–related factors, including cyclin D1, proliferating cell nuclear antigen, and cleaved caspase-3, were increased in the hippocampus of Tg-PS2m, whereas TE reversed their altered expression. Conclusions The results support the hypothesis that the pathologic features and behavioral symptoms of AD caused by accumulation of amyloid β-peptide in hippocampus, causing aberrant cell cycle reentry and apoptosis, can be reversed by regular exercise.
Type of Medium:
Online Resource
ISSN:
1530-0315
,
0195-9131
DOI:
10.1249/MSS.0000000000002834
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2031167-9
SSG:
31
