Affiliations: [a] State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China | [b] Laboratory of Biotechnology and State Key Laboratory of Chinese Ethnic Minority Traditional Medicine, College of Life and Environmental Science, Minzu University of China, Beijing, China | [c] Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China | [d] Shenzhen Key Lab of Neuropsychiatric Modulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
Correspondence:
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Correspondence to: Yan Zhang, Ph.D., (E-mail: [email protected]); Nan Sui, Ph.D., (E-mail: [email protected]); and Xiaoyan Qin, Ph.D., (E-mail: [email protected]), College of Life Sciences, Room 219, Peking University, Beijing 100871, China. Tel.: +86 10 62754880; Fax: +86 10 62751526.
Abstract: 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 AβPP/PS1 mouse brains. GABA downregulated amyloid-β (Aβ) uptake in neurons through the receptor for advanced glycation end-products. Therefore, relative high levels of GABA decreased cytotoxicity induced by Aβ in WT mice. GABA treatment decreased basal levels of cell death and the cell death induced by hydrogen peroxide in WT and AβPP/PS1 neurons. Application of GABA during early life before 2 months of age can improve cognitive function significantly in AβPP/PS1 mice. However, GABA treatment at 6 and 8 months of age cannot improve water maze performance. Activating or suppressing GABAA receptors by optogenetic methods also confirmed that GABA activation before 2 months of age increased water maze performance in AβPP/PS1 mice. Our data suggest that GABA administration during early life can be a potential treatment for AD.
