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GABA Attenuates Amyloid Toxicity by Downregulating its Endocytosis and Improves Cognitive Impairment
Sun, Xiaqin1; Meng, Xiaolu4; Zhang, Jie5; Li, Yonghui4; Wang, Liping5; Qin, Xiaoyan2,3; Sui, Nan4; Zhang, Yan1; Zhang, Y (reprint author), Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Room 219, Beijing 100871, Peoples R China.
2012
发表期刊JOURNAL OF ALZHEIMERS DISEASE
ISSN1387-2877
文章类型Article
卷号31期号:3页码:635-649
产权排序3
摘要GABA (gamma-aminobutyric acid) receptor modulators have been investigated as a potential treatment strategy in Alzheimer's disease (AD). In the present study, we found that GABA levels were different in wild type (WT) and A beta PP/PS1 mouse brains. GABA downregulated amyloid-beta (A beta) uptake in neurons through the receptor for advanced glycation end-products. Therefore, relative high levels of GABA decreased cytotoxicity induced by A beta in WT mice. GABA treatment decreased basal levels of cell death and the cell death induced by hydrogen peroxide in WT and A beta PP/PS1 neurons. Application of GABA during early life before 2 months of age can improve cognitive function significantly in A beta PP/PS1 mice. However, GABA treatment at 6 and 8 months of age cannot improve water maze performance. Activating or suppressing GABA(A) receptors by optogenetic methods also confirmed that GABA activation before 2 months of age increased water maze performance in A beta PP/PS1 mice. Our data suggest that GABA administration during early life can be a potential treatment for AD.
关键词Amyloid-beta cell death cognitive impairment endocytosis GABA
学科领域Cognitive Psychology,Medical Psychology
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收录类别SCI
语种英语
项目资助者National Program of Basic Research ; Ministry of Science and Technology of China [2009CB941301] ; National Science Foundation of China (NSFC) Major Research Grant [91132718] ; Roche Research Grant ; Peking University President Research Grant ; Ministry of Education Recruiting Research Grant ; 973 Program [2009CB522002] ; National Natural Science Foundation China [31170988] ; 985 project [MUC98504-1, MUC98507-08] ; Hundred Talents Program ; Instrument Developing Project of the Chinese Academy of Sciences [2010019]
项目简介This work was supported by the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2009CB941301), National Science Foundation of China (NSFC) Major Research Grant (91132718), Roche Research Grant, Peking University President Research Grant and Ministry of Education Recruiting Research Grant to YZ, 973 Program (2009CB522002) to NS, National Natural Science Foundation China (31170988) to NS, 985 project (MUC98504-1, MUC98507-08) to XQ, "Hundred Talents Program" and the Instrument Developing Project of the Chinese Academy of Sciences (Grant No. 2010019) to LW.
WOS记录号WOS:000308197000016
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文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/12827
专题中国科学院心理健康重点实验室
通讯作者Zhang, Y (reprint author), Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Room 219, Beijing 100871, Peoples R China.
作者单位1.Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China
2.Minzu Univ China, Coll Life & Environm Sci, Biotechnol Lab, Beijing, Peoples R China
3.Minzu Univ China, Coll Life & Environm Sci, State Key Lab Chinese Ethn Minor Tradit Med, Beijing, Peoples R China
4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
5.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Neuropsychiat Modulat, Shenzhen, Peoples R China
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GB/T 7714
Sun, Xiaqin,Meng, Xiaolu,Zhang, Jie,et al. GABA Attenuates Amyloid Toxicity by Downregulating its Endocytosis and Improves Cognitive Impairment[J]. JOURNAL OF ALZHEIMERS DISEASE,2012,31(3):635-649.
APA Sun, Xiaqin.,Meng, Xiaolu.,Zhang, Jie.,Li, Yonghui.,Wang, Liping.,...&Zhang, Y .(2012).GABA Attenuates Amyloid Toxicity by Downregulating its Endocytosis and Improves Cognitive Impairment.JOURNAL OF ALZHEIMERS DISEASE,31(3),635-649.
MLA Sun, Xiaqin,et al."GABA Attenuates Amyloid Toxicity by Downregulating its Endocytosis and Improves Cognitive Impairment".JOURNAL OF ALZHEIMERS DISEASE 31.3(2012):635-649.
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