Journal
NEUROSCIENCE RESEARCH
Volume 69, Issue 2, Pages 161-173Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neures.2010.10.004
Keywords
Alzheimer's disease; beta-Amyloid; MAPK; Tau; Corticosterone; Neuronal cell death
Categories
Funding
- National Research Foundation [G00036 (102282)]
- National Research Foundation of Korea [2008-313-G00036] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 A beta-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-3 alpha/beta. 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. A beta-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 A beta-42 and neuronal death pathways. Therefore, treadmill exercise may be beneficial in prevention or treatment of AD. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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