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http://dx.doi.org/10.5352/JLS.2010.20.3.444

The Effects of Treadmill Exercise on Cognitive Performance, Brain Mitochondrial Aβ-42, Cytochrome c, SOD-1, 2 and Sirt-3 Protein Expression in Mutant (N141I) Presenilin-2 Transgenic Mice of Alzheimer's Disease  

Koo, Jung-Hoon (Exercise Biochemistry Laboratory, Korea National Sport University)
Eum, Hyun-Sub (Exercise Biochemistry Laboratory, Korea National Sport University)
Kang, Eun-Bum (Exercise Biochemistry Laboratory, Korea National Sport University)
Kwon, In-Su (Exercise Biochemistry Laboratory, Korea National Sport University)
Yeom, Dong-Cheol (Exercise Biochemistry Laboratory, Korea National Sport University)
An, Gil-Young (Exercise Biochemistry Laboratory, Korea National Sport University)
Oh, Yoo-Sung (Department of Sport Information, Seoul City University)
Baik, Young-Soo (Department of Physical Education, Kun-Yang University)
Cho, In-Ho (Exercise Biochemistry Laboratory, Korea National Sport University)
Cho, Joon-Yong (Exercise Biochemistry Laboratory, Korea National Sport University)
Publication Information
Journal of Life Science / v.20, no.3, 2010 , pp. 444-452 More about this Journal
Abstract
The purpose of this study was to investigate the effects of treadmill exercise on $A{\beta}$-42, cytochrome c, SOD-1, 2 and Sirt-3 protein expressions in brain cytosol and mitochondria in mutant (N141I) presenilin-2 transgenic mice with Alzheimer's disease (AD). The mice were divided into four groups (Non-Tg-sedentary, n=5; Non-Tg treadmill exercise, n=5; Tg-sedentary, n=5; Tg treadmill exercise, n=5). To evaluate the neuroprotective effect of treadmill exercise, Non-Tg and Tg mice were subjected to exercise training on a treadmill for 12 wk, after which their brain cytosol and mitochondria were evaluated to determine whether any changes in the cognitive performance, $A{\beta}$-42 protein, cytochrome c protein, anti-oxidant enzymes (SOD-1, SOD-2) and Sirt-3 protein had occurred. The results indicated that treadmill exercise resulted in amelioration in cognitive deficits of Tg mice. In addition, the expressions of mitochondrial $A{\beta}$-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-l and SOD-2 were significantly increased in response to treadmill exercise. Furthermore, treadmill exercise significantly increased the expression of Sirt-3 protein in Non-Tg and Tg mice. Taken together, these results suggest that treadmill exercise is a simple behavioral intervention which can sufficiently improve cognitive performance and inhibit $A{\beta}$-induced oxidative stress in AD.
Keywords
Alzheimer's disease (AD); $\beta$-amyloid-42($A{\beta}$-42); anti-oxidant enzyme-1, 2 (SOD-1, 2); silent information regulator-3 (Sirt-3); presenilin-2 (PS-2); treadmill exercise;
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1 Qin, W., T. Yang, L. Ho, Z. Zhao, J. Wang, L. Chen, W. Zhao, M. Thiyagarajan, D. MacGrogan, J. T. Rodgers, P. Puigserver, J. Sadoshima, H. Deng, S. Pedrini, S. Gandy, A. A. Sauve, and G. M. Pasinetti. 2006. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J. Biol. Chem. 281, 21745-21754.   DOI
2 Reddy, P. H. 2006. Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease. J. Neurochem. 96, 1-13.   DOI
3 Reddy, P. H. 2007. Mitochondrial dysfunction in aging and Alzheimer's disease: strategies to protect neurons. Antioxid Redox. Signal. 9, 1647-1658.   DOI
4 Schuessel, K., S. Schafer, T. A. Bayer, C. Czech, L. Pradier, F. Muller-Spahn, W. E. Muller, and A. Eckert. 2005. Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol. Dis. 18, 89-99.   DOI
5 Shi, T., F. Wang, E. Stieren, and Q. Tong. 2005. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J. Biol. Chem. 280, 13560–13567.
6 Takuma, K., J. Yao, J. Huang, H. Xu, Z. Chen, J. Luddy, A. C. Trillat, D. M. Stern, O. Arancio, and S. S. Yan. 2005. ABAD enhances Abetainducedcell stress via mitochondrial dysfunction. FASEB. J. 19, 597–598.
7 Tanzi, R. E., D. M. Kovacs, T. W. Kim, R. D. Moir, S. Y. Guenette, W. Wasco. 1996. The gene defects responsible for familial Alzheimer's disease. Neurobiol. Dis. 3 159-68.   DOI
8 Um, H. S., E. B. Kang, Y. H. Leem, I. H. Cho, C. H. Yang, K. R. Chae, D. Y. Hwang, and J. Y Cho. 2008. Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model. Int. J. Mol. Med. 22, 529-539.
9 Lombard, D. B., F. W. Alt, H. L. Cheng, J. Bunkenborg, R. S. Streeper, R. Mostoslavsky, J. Kim, G. Yancopoulos, D. Valenzuela, and Aet. Murphy. 2007. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell Biol. 27, 8807-8814.   DOI
10 Lustbader, J. W., M. Cirilli, C. Lin, H. W. Xu, K. Takuma, N. Wang, C. Caspersen, X. Chen, S. Pollak, M. Chaney, F. Trinchese, S. Liu, F. Gunn-Moore, L. F. Lue, D. G. Walker, P. Kuppusamy, Z. L. Zewier, O. Arancio, D. Stern, S. S. Yan, and Wu, H. 2004. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 304, 448-452.   DOI
11 Neeper, S. A., F. Gomez-Pinilla, J. Choi, and C. W. Cotman. 1996. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 726, 49-56.   DOI
12 Nichol, K. E., W. W. Poon, A. I. Parachikova, D. H. Cribbs, C. G. Glabe, and C. W. Cotman. 2008. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased mice. J. Neuroinflammation. 9, 5-13.
13 Qin, W., M. Chachich, M. Lane, G. Roth, M. Bryant, R. de Cabo, M. A. Ottinger, J. Mattison, D. Ingram, S. Gandy, and G. M. Pasinetti. 2006. Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). J. Alzheimers. 10, 417-422.
14 Noor, R., S. Mittal, and J. Iqbal. 2002. Superoxide dismutase--applications and relevance to human diseases. Med. Sci. Monit. 8, 210-5.
15 Ohsawa, I., K. Nishimaki, C. Yasuda, K. Kamino, and S. Ohta. 2003. Deficiency in a mitochondrial aldehyde dehydrogenase increases vulnerability to oxidative stress in PC12 cells. J. Neurochem. 84, 1110-1117.   DOI
16 Onyango, P., I. Celic, J. M. McCaffery, J. D. Boeke, and A. P. Feinberg. 2002. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc. Natl. Acad. Sci. USA 99, 13653-13658.   DOI
17 Hansson Petersen, C. A., N. Alikhani, H. Behbahani, B. Wiehager, P. F. Pavlov, I. Alafuzoff, V. Leinonen, A. Ito, B. Winblad, E. Glaser, and M. Ankarcrona. 2008. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc. Natl. Acad. Sci. USA 105, 13145-13150.   DOI
18 Hardy, J. A. and G. A. Higgins. 1992. Alzheimer's disease: the amyloid cascade hypothesis. Science 256, 184-195.   DOI
19 Hwang, D. Y., K. R. Chae, T. S. Kang, J. H. Hwang, C. H. Lim, H. K. Kang, J. S. Goo, M. R. Lee, H. J. Lim, S. H. Min, J. Y. Cho, J. T. Hong, C. W. Song, S. G. Paik, J. S. Cho, and Y. K. Kim. 2002. Alterations in behavior, amyloid beta-42, caspase-3, and Cox-2 in mutant PS2 transgenic mouse model of Alzheimer's disease. FASEB. J. 16, 805-813.   DOI
20 Kienlen-Campard, P., S. Miolet, B. Tasiaux, and J. N. Octave. 2002. Intracellular amyloid-beta (1-42), but not extracellular solubleamyloid-beta peptides, induces neuronal apoptosis. J. Biol. Chem. 277, 15666-15670.   DOI
21 Li, F., N. Y. Calingasan, F. Yu, W. M. Mauck, M. Toidze, C. G. Almeida, R. H. Takahashi, G. A. Carlson, M. Flint Beal, M. T. Lin, and G. K. Gouras. Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J. Neurochem. 89, 1308-1312.   DOI
22 Knobloch, M., U. Konietzko, D. C. Krebs, and R. M. Nitsch. 2007. Intracellular Abeta and cognitive deficits precede beta-amyloid deposition in transgenic arcAbeta mice. Neurobiol. Aging. 28, 1297-1306.   DOI
23 LaFerla, F. M., K. N. Green, and S. Oddo. 2007. Intracellular amyloid-beta in Alzheimer's disease. Nat. Rev. Neurosci. 8, 499-509.   DOI
24 Lee, V. M. and J. Q. Trojanowski. 1992. The disordered neuronal cytoskeleton in Alzheimer's disease. Curr. Opin. Neurobiol. 2, 653-656.   DOI
25 Behl, C., J. B. Davis, R. Lesley, and D. Schubert. 1994. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77, 817-827.   DOI
26 Blander, G. and L. Guarente. 2004. The Sir2 family of protein deacetylases. Annu. Rev. Biochem. 73, 417-435.   DOI
27 Books, G. A. and T. P. White. 1978. Determination of metabolic and heart rate responses of rats to treadmill exercise. J. Appl. Physiol. 45, 1009-1015.
28 Bradford, L. W. 1976. Problems of ethics and behavior in the forensic sciences. J. Forensic. Sci. 21, 763-768.
29 Bush, A. I., C. S Satwood, L. E. Goldstein, X. Huang, and J. Rogers. 2000. Could Abeta and AbetaPP be antioxidants? Journal of Alzheimers Disease 2, 83-84.
30 Casley, C. S., L. Canevari, J. M. Land, J. B. Clark, and M. A. Sharpe. 2002. Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J. Neurochem. 80, 91-100.   DOI
31 Frye, R. A. 2000. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun. 273, 793-808.   DOI
32 Chen, J. X. and S. D. Yan. 2007. Pathogenic role of mitochondrial [correction of mitochondral] amyloid-beta peptide. Expert Rev. Neurother. 7, 1517-25.   DOI
33 Cho, J. Y., D. Y. Hwang, T. S. Kang, D. H. Shin, J. H. Hwang, C. H. Lim, S. H. Lee, H. J. Lim, S. H. Min, S. J. Seo, Y. S. Song, K. T. Nam, K. S. Lee, J. S. Cho, and Y. K. Kim. 2003. Use of NSE/PS2m-transgenic mice in the study of the protective effect of exercise on Alzheimer's disease. J. Sports Sci. 21, 943-951.   DOI
34 Cho, J. Y., H. S. Um, E. B. Kang, I. H. Cho, C. H. Kim, J. S. Cho, and D. Y. Hwang. 2010. The combination of exercise training and $\alpha$-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice. Int. J. Mol. Med. 25, 337-346.
35 Yuede, C. M., S. D. Zimmerman, H. Dong, M. J. Kling, A. W. Bero, D. M. Holtzman, B. F. Timson, and J. G. Csernansky. 2009. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease. Neurobiol. Dis. 35, 426-432.   DOI
36 Adlard, P. A., V. M. Perreau, V. Pop, and C. W. Cotman. 2005. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. J. Neurosci. 25, 4217-4221.   DOI
37 Anantharaman, M., J. Tangpong, J. N. Keller, M. P. Murphy, W. R. Markesbery, K. K. Kiningham, and D. K. St Clair. 2006. Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease. Am. J. Pathol. 168, 1608-1718.   DOI
38 Van Praag, H., P. M. Qu, R. C. Elliott, H. Wu, C. F. Dreyfus, and I. B. Black. 1998. Unilateral hippocampal lesions in newborn and adult rats: effects on spatial memory and BDNF gene expression. Behav. Brain Res. 92, 21-30.   DOI