Browse > Article
http://dx.doi.org/10.5352/JLS.2008.18.6.796

The Effect of Exercise Training on Aβ-42, BDNF, GLUT-1 and HSP-70 Proteins in a NSE/ APPsw-transgenic Model for Alzheimer's Disease.  

Eum, Hyun-Sub (Exercise Biochemistry Laboratory, Korea National Sport University)
Kang, Eun-Bum (Exercise Biochemistry Laboratory, Korea National Sport University)
Lim, Yea-Hyun (Exercise Biochemistry Laboratory, Korea National Sport University)
Lee, Jong-Rok (Exercise Biochemistry Laboratory, Korea National Sport University)
Cho, In-Ho (Exercise Biochemistry Laboratory, Korea National Sport University)
Kim, Young-Soo (Korea Institute of Sport Science)
Chae, Kab-Ryoung (Division of Laboratory Animal Resources, and National Institute of Toxicological Research, Korea FDA)
Hwang, Dae-Yean (College of National Resources & Life Science, Pusan National University)
Kwak, Yi-Sub (Department of Physical Education, Dong-Eui University)
Oh, Yoo-Sung (Department of Physical Education, Seoul City University)
Cho, Joon-Yong (Exercise Biochemistry Laboratory, Korea National Sport University)
Publication Information
Journal of Life Science / v.18, no.6, 2008 , pp. 796-803 More about this Journal
Abstract
Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.
Keywords
Alzheimer's disease (AD); amyloid ${\beta}-42$ ($A{\beta}-42$); heat shock protein-70 (HSP-70); glucose transporter-1 (GLUT-1); brain derived neurotropic factor (BDNF); endurance exercise training;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Rogaev, E. I., R. Sherrington, E. A. Rogaeva, G. Levesque, M. Ikeda, Y. Liang, H. Chi, C. Lin, K. Holman, T. Tsuda. 1995. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778   DOI   ScienceOn
2 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   ScienceOn
3 Chong, Z. Z., F. Li and K. Maiese. 2005. Oxidative stress in the brain: novel cellular targets that govern survival during neurodegenerative disease. Prog. Neurobiol. 75, 207-246   DOI   ScienceOn
4 Ding, Y. H., J. Li, Y. Zhou, J. A. Rafols, J. C. Clark and Y. Ding. 2006. Cerebral angiogenesis and expression of angiogenic factors in aging rats after exercise. Curr. Neurovasc. Res. 3, 15-23   DOI   ScienceOn
5 Hsiao, K., P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang and G. Cole. 1996. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99-102   DOI   ScienceOn
6 Hwang, D. Y., J. S. Cho, S. H. Lee, K. R. Chae, H. J. Lim, S. H. Min, S. J. Seo, Y. S. Song, C. W. Song, S. G. Paik, Y. Y. Sheen and Y. K. Kim. 2004. Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw. Exp. Neurol. 186, 20-32   DOI   ScienceOn
7 Lazarov, O., J. Robinson, Y. P. Tang, I. S. Hairston, Z. Korade-Mirnics, V. M. Lee, L. B. Hersh, R. M. Sapolsky, K. Mirnics and S. S Sisodia. 2005. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120, 701-713   DOI   ScienceOn
8 Lee, V. M. and J. Q. Trojanowski. 1992. The disordered neuronal cytoskeleton in Alzheimer's disease. Curr. Opin. Neurobiol. 2, 653-656   DOI   ScienceOn
9 Spirduso, W. W. 1983. Exercise and the Aging Brain. (The 1982 CH McCloy Research Lecture), pp. 208-218
10 van Praag, H., G. Kempermann and F. H. Gage. 1999. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266-270   DOI   ScienceOn
11 Farkas, E. and P. G. Luiten. 2001. Cerebral microvascular pathology in aging and Alzheimer's disease. Prog. Neurobiol. 64, 575-611   DOI   ScienceOn
12 Hager, K., A. Marahrens, M. Kenklies, P. Riederer and G. Munch. 2001. Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Arch. Gerontol. Geriatr. 32, 275-282   DOI   ScienceOn
13 Melling, C. W., D. B. Thorp, K. J. Milne, M. P. Krause and E. G. Noble. 2007. Exercise-mediated regulation of Hsp70 expression following aerobic exercise training. Am. J. Physiol. Heart Circ. Physiol. 293, H3692-3698   DOI   ScienceOn
14 Russo-Neustadt, A. A., H. Alejandre, C. Garcia, A. S. Ivy and M. J. Chen. 2004. Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology 29, 2189-2199   DOI   ScienceOn
15 Tanzi, R. E., D. M. Kovacs, T. W. Kim, R. D. Moir, S. Y. Guenette and W. Wasco, 1996. The gene defects responsible for familial Alzheimer's disease. Neurobiol. Dis. 3, 159-168   DOI   ScienceOn
16 Yoo, B. C., S. H. Kim, N. Cairns, M. Fountoulakis and G. Lubec. 2001. Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease. Biochem. Biophys. Res. Commun. 280, 249-258   DOI   ScienceOn
17 Horwood, N. and D. C. Davies. 1994. Immunolabelling of hippocampal microvessel glucose transporter protein is reduced in Alzheimer's disease. Virchows Arch. 425, 69-72
18 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   ScienceOn
19 Black, J. E., K. R. Isaacs and W. T. Greenough. 1991. Usual vs. successful aging: some notes on experiential factors. Neurobiol. Aging 12, 325-328   DOI   ScienceOn
20 Hock, C., K. Heese, C. Hulette, C. Rosenberg and U. Otten. 2000. Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch. Neurol. 57, 846-851   DOI   ScienceOn
21 Xie, L., E. Helmerhorst, K. Taddei, B. Plewright, W. van Bronswijk and R. Martins. 2002. Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor. J. Neurosci. 22, RC221   DOI
22 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   ScienceOn
23 Cotman, C. W., N. C. Berchtold and L. A. Christie. 2007. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 30, 464-472   DOI   ScienceOn
24 Kumar, P., R. K. Ambasta, V. Veereshwarayya, K. M. Rosen, K. S. Kosik, H. Band, R. Mestril, C. Patterson and H. W. Querfurth. 2007. CHIP and HSPs interact with beta- APP in a proteasome-dependent manner and influence Abeta metabolism. Hum. Mol. Genet. 16, 848-864   DOI   ScienceOn
25 Nichol, K. E., A. I. Parachikova and C. W. Cotman. 2007. Three weeks of running wheel exposure improves cognitive performance in the aged Tg2576 mouse. Behav. Brain Res. 184, 124-132   DOI   ScienceOn
26 Cotman, C. W. and N. C. Berchtold. 2002. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 25, 295-301   DOI   ScienceOn
27 Wolf, S. A., G. Kronenberg, K. Lehmann, A. Blankenship, R. Overall, M. Staufenbiel and G. Kempermann. 2006. Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease. Biol. Psychiatry. 60, 1314-1323   DOI   ScienceOn
28 Korea Institute and Social Affairs, 2007
29 Hooijmans, C. R., C. Graven, P. J. Dederen, H. Tanila, T. van Groen and A. J. Kiliaan. 2007. Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res. 1181, 93-103   DOI   ScienceOn
30 Blass, J. P. 2001. Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J. Neurosci. Res. 66, 851-856   DOI   ScienceOn
31 Yenari, M. A., J. Liu, Z. Zheng, Z. S. Vexler, J. E. Lee and R. G. Giffard. 2005. Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. Ann. N.Y. Acad. Sci. 1053, 74-83   DOI   ScienceOn
32 Choeiri, C., W. Staines and C. Messier. 2002. Immunohistochemical localization and quantification of glucose transporters in the mouse brain. Neuroscience 111, 19-34   DOI   ScienceOn