mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease

Ma,Yun-Qing; Wu,Dong-Ke; Liu,Jian-Kun

doi:10.3892/mmr.2012.1186

mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease

Authors:
- Yun-Qing Ma
- Dong-Ke Wu
- Jian-Kun Liu
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Affiliations: Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China
Published online on: November 15, 2012 https://doi.org/10.3892/mmr.2012.1186
Pages: 623-627

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Abstract

This study explored the effects of mammalian target of rapamycin (mTOR) on the increased risk of developing Alzheimer's disease (AD) in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley rats were randomly divided into four groups: control, T2DM, AD and T2DM+AD. Changes in the learning and memory abilities of the rats were observed using the Morris water maze. mTOR activity and tau protein hyperphosphorylation in the hippocampus were analyzed by immunohistochemical staining and RT-PCR. The learning and memory abilities of the experimental rats were weakened compared with those of the control group. The T2DM+AD group revealed significant changes over the T2DM and AD groups. Compared with the control, T2DM and AD groups, the mTOR protein and mRNA levels, hyperphosphorylation of tau protein and total tau protein mRNA levels were significantly increased in the T2DM+AD group. T2DM may excessively activate mTOR in the hippocampal tissue by impairing insulin signaling, thereby increasing the extent of tau hyperphosphorylation and promoting the occurrence of AD.

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1	Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC and Butler PC: Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 53:474–481. 2004. View Article : Google Scholar : PubMed/NCBI
2	Moroz N, Tong M, Longato L, Xu H and de la Monte SM: Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus. J Alzheimers Dis. 15:29–44. 2008.PubMed/NCBI
3	Bao CR, Zhou M and Qin DL: Present situation of studies about the relationship between type 2 diabetes and Alzheimer’s disease. J Luzhou Medical College. 32:568–569. 2009.(In Chinese).
4	Zhu XY, Niu BF, Dong ZX and Huang HY: Studies of the relationship between type 2 diabetes and Alzheimer’s disease. Medical Review. 17:1528–1531. 2011.
5	Chen YJ and Tian JZ: Alzheimer’s disease is another form of diabetes. Chin J Gerontology. 28:402–406. 2008.(In Chinese).
6	de la Monte SM and Wands JR: Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimer Disease. 7:45–61. 2005.PubMed/NCBI
7	Li Y: The awareness of the relationship between Central insulin resistance and Alzheimer’s disease. J Diagn Pract. 8:248–251. 2009.
8	Leibowitz G, Cerasi E and Ketzinel-Gilad M: The role of mTOR in the adaptation and failure of beta-cells in type 2 diabetes. Diabetes. 10(Suppl 4): 157–169. 2008.PubMed/NCBI
9	Glynn EL, Lujan HL, Kramer VJ, Drummond MJ, DiCarlo SE and Rasmussen BB: A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle. Appl Physiol Nutr Metab. 33:93–101. 2008. View Article : Google Scholar : PubMed/NCBI
10	Vila-Bedmar R, Lorenzo M and Fernández-Veledo S: Adenosine 5′-monophosphate-activated protein kinase-mammalian target of rapamycin cross talk regulates brown adipocyte differ- entiation. Endocrinology. 151:980–992. 2010.
11	Zhang C, Yoon MS and Chen J: Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes. Am J Physiol Endocrinol Metab. 296:E862–E868. 2009. View Article : Google Scholar : PubMed/NCBI
12	Fan H: The research progress of risk-related between diabetes and Alzheimer’s disease. J Practical Geriatrics. 24:342–345. 2010.
13	Mi K and Johnson GV: The role of Tau phosphorylation in the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res. 3:449–463. 2006.
14	An WL, Cowburn RF, Li L, et al: Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer’s disease. Am J Pathol. 163:591–607. 2003.PubMed/NCBI
15	Khurana V, Lu Y, Steinhilb ML, Oldham S, Shulman JM and Feany MB: TOR-mediated cell-cyele activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol. 16:230–241. 2006. View Article : Google Scholar : PubMed/NCBI
16	Zhang Y, Zhang Sl, Gao FH, Chen Y and Yang XJ: The research of GSK-3β and tau phosphorylated proteins in hippocampal tissue of type 2 diabetes and Alzheimer’s disease rats. Chin J Gerontol. 29:63–66. 2010.(In Chinese).