Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer's disease.
The present study was undertaken to further investigate the protective effect of treadmill exercise on the hippocampal proteins associated with neuronal cell death in an aged transgenic (Tg) mice with Alzheimer's disease (AD). To address this, Tg mouse model of AD, Tg-NSE/PS2m, which expresses human mutant PS2 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. The exercised mice were treadmill run at speed of 12 m/min, 60 min/day, 5 days/week on a 0% gradient for 3 months. Treadmill exercised mice improved cognitive function in water maze test. Treadmill exercised mice significantly reduced the expression of Aβ-42, Cox-2, and caspase-3 in the hippocampus. In parallel, treadmill exercised Tg mice decreased the phosphorylation levels of JNK, p38MAPK and tau (Ser404, Ser202, Thr231), and increased the phosphorylation levels of ERK, PI3K, Akt and GSK-3α/β. In addition, treadmill exercised Tg mice up-regulated the expressions of NGF, BDNF and phospho-CREB, and the expressions of SOD-1, SOD-2 and HSP-70. Treadmill exercised Tg mice up-regulated the expression of Bcl-2, and down-regulated the expressions of cytochrome c and Bax in the hippocampus. The number of TUNEL-positive cells in the hippocampus in mice was significantly decreased after treadmill exercise. Finally, serum TC, insulin, glucose, and corticosterone levels were significantly decreased in the Tg mice after treadmill exercise. As a consequence of such change, Aβ-dependent neuronal cell death in the hippocampus of Tg mice was markedly suppressed following treadmill exercise. These results strongly suggest that treadmill exercise provides a therapeutic potential to inhibit both Aβ-42 and neuronal death pathways. Therefore, treadmill exercise may be beneficial in prevention or treatment of AD.
Department of Exercise Prescription, Kon-Yang University, 119 Daehangro, Nonsan city, Chungnam 320-711, Republic of Korea.
Hyun-Sub
HS
Um
Eun-Bum
EB
Kang
Jung-Hoon
JH
Koo
Hyun-Tae
HT
Kim
Jin-Lee
Eung-Joon
EJ
Kim
Chun-Ho
CH
Yang
Gil-Young
GY
An
In-Ho
IH
Cho
Joon-Yong
JY
Cho
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology