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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
Source PublicationJOURNAL OF ALZHEIMERS DISEASE
ISSN1387-2877
SubtypeArticle
Volume31Issue:3Pages:635-649
Contribution Rank3
AbstractGABA (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.
KeywordAmyloid-beta cell death cognitive impairment endocytosis GABA
Subject AreaCognitive Psychology,Medical Psychology
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Indexed BySCI
Language英语
Funding OrganizationNational 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]
Project Intro.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 IDWOS:000308197000016
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/12827
Collection中国科学院心理健康重点实验室
Corresponding AuthorZhang, Y (reprint author), Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Room 219, Beijing 100871, Peoples R China.
Affiliation1.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
Recommended Citation
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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