TY - JOUR
T1 - Exercise Reverses Amyloid β-Peptide-Mediated Cognitive Deficits in Alzheimer's Disease Mice Expressing Mutant Presenilin-2
AU - Hwang, Dong Joo
AU - Choi, Dong Hun
AU - Kwon, Ki Chun
AU - Kim, Eon Ho
AU - Kim, Tae Kyung
AU - Koo, Jung Hoon
AU - Cho, Joon Yong
N1 - Publisher Copyright:
© Lippincott Williams & Wilkins.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Purpose 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.
AB - Purpose 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.
KW - APOPTOSIS
KW - CELL CYCLE REENTRY
KW - PRESENILIN-2
KW - β-AMYLOID
UR - http://www.scopus.com/inward/record.url?scp=85126490705&partnerID=8YFLogxK
U2 - 10.1249/MSS.0000000000002834
DO - 10.1249/MSS.0000000000002834
M3 - Article
C2 - 34816813
AN - SCOPUS:85126490705
SN - 0195-9131
VL - 54
SP - 551
EP - 565
JO - Medicine and Science in Sports and Exercise
JF - Medicine and Science in Sports and Exercise
IS - 4
ER -