title: Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice.
abstract: Previously our study has demonstrated that long-term treadmill exercise improved cognitive deficit in APP/PS1 transgenic mice of Alzheimer's disease (AD) paralleled by enhanced long-term potentiation (LTP). The present study was undertaken to further investigate whether the treadmill running could inhibit the progression of Alzheimer's disease (AD)-like neuropathology in hippocampus of the APP/PS1 mouse models of AD, and to define a potential molecular mechanism underlying the exercise-induced reduction in AD-like neuropathology. Five months of treadmill exercise resulted in a robust reduction in β-amyloid (Aβ) deposition and tau phosphorylation in the hippocampus of APP/PS1 mice. This was accompanied by a significant decrease in APP phosphorylation and PS1 expression. We also observed GSK3, rather than CDK5, was inhibited by treadmill exercise. These results indicate that treadmill exercise is sufficient to inhibit the progression of AD-like neuropathology in the hippocampus of APP/PS1 transgenic mouse model, and may mediate APP processing in favor of reduced Aβ deposition. In addition, we demonstrate that treadmill exercise attenuates AD-like neuropathology in AD transgenic mice via a GSK3 dependent signaling pathway.
authors: Department of Sports Medicine, China Medical University, Shenyang 110001, People's Republic of China. Electronic address: liuhuili77@hotmail.com.
authors: Hui-li
authors: HL
authors: Liu
authors: Gang
authors: G
authors: Zhao
authors: He
authors: H
authors: Zhang
authors: Li-de
authors: LD
authors: Shi
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D010805:Physical Conditioning, Animal; D058225:Plaque, Amyloid / Q000503:physiopathology / Q000517:prevention & control; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C558298:Mapt protein, mouse; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: APP/PS1 transgenic mice; Alzheimer's disease; Glycogen synthase kinase 3; Tau; Treadmill exercise; β-Amyloid