Alternations of central insulin-like growth factor-1 sensitivity in APP/PS1 transgenic mice and neuronal models
文献类型：期刊论文
| 作者 | Zhang, Bing; Tang, Xi Can; Zhang, Hai Yan |
| 刊名 | JOURNAL OF NEUROSCIENCE RESEARCH
 |
| 出版日期 | 2013-05 |
| 卷号 | 91期号:5页码:717-725 |
| 关键词 | Alzheimer's disease insulin-like growth factor-1 beta-amyloid APP/PS1 mice |
| ISSN号 | 0360-4012 |
| DOI | 10.1002/jnr.23201 |
| 文献子类 | Article |
| 英文摘要 | Although many post-mortem studies have found evidence of central insulin resistance in Alzheimer's disease (AD) patients, results on changes of central insulin-like growth factor-1 (IGF-1) signaling in the pathological process of AD remain controversial. In the present study, we observed the activation states of IGF-1 downstream signaling in brain slices of transgenic mice carrying APPswe/PS1dE9 mutations (APP/PS1 mice) at both early and late stages (ex vivo) and further investigated the involvement of oligomeric -amyloid (A) and A-enriched culture medium (CM) on IGF-1 sensitivity employing neuronal models (in vitro). In 6- and 18-month-old APP/PS1 mice, the phosphorylations of IGF-1 receptor (IGF-1R) and Akt in response to IGF-1 stimulation were significantly reduced in the hippocampal and cortical slices, whereas IGF-1R protein expression and mRNA levels of IGF-1 and IGF-1R in the hippocampal slices were significantly higher than that in wild-type mice. In agreement with these results, reduced IGF-1 sensitivity was verified in APP and PS1 double stably transfected CHO cells; moreover, IGF-1 stimulated phosphorylations of IGF-1R and Akt were also markedly weakened by oligomeric A or A-enriched CM posttreatment in CHO cells without APP/PS1-transfected (K1 cells) and primary hippocampal neurons. These observations indicate that the impaired central IGF-1 sensitivity at early and late stages of APP/PS1 transgenic mice might be attributable, at least partially, to the overproduced A, especially the oligomeric A. These findings may shed new light on the mechanisms underlying the defective IGF-1 signaling in AD pathogenesis and provide important clues for AD drug discovery. (c) 2013 Wiley Periodicals, Inc. |
| WOS关键词 | ALZHEIMERS-DISEASE PATIENTS ; A-BETA OLIGOMERS ; FACTOR EXPRESSION ; KINASE-B ; BRAIN ; RECEPTOR ; PROTEIN ; ACETYLCHOLINE ; MECHANISMS ; RESISTANCE |
| 资助项目 | Ministry of Science and Technology of China[2011CB510004] ; National Natural Science Foundation of China[81173034] ; National Natural Science Foundation of China[81072646] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2012ZX09301-001-004] ; SKLDR/SIMM Projects[SIMM1105KF-04] ; SKLDR/SIMM Projects[SIMM 1203ZZ-03] ; Shanghai Science and Technology Development Funds[10QA1408100] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000315968700010 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277646]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Hai Yan |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Bing,Tang, Xi Can,Zhang, Hai Yan. Alternations of central insulin-like growth factor-1 sensitivity in APP/PS1 transgenic mice and neuronal models[J]. JOURNAL OF NEUROSCIENCE RESEARCH,2013,91(5):717-725. |
| APA | Zhang, Bing,Tang, Xi Can,&Zhang, Hai Yan.(2013).Alternations of central insulin-like growth factor-1 sensitivity in APP/PS1 transgenic mice and neuronal models.JOURNAL OF NEUROSCIENCE RESEARCH,91(5),717-725. |
| MLA | Zhang, Bing,et al."Alternations of central insulin-like growth factor-1 sensitivity in APP/PS1 transgenic mice and neuronal models".JOURNAL OF NEUROSCIENCE RESEARCH 91.5(2013):717-725. |
入库方式： OAI收割
来源：上海药物研究所
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