中国科学院心理健康重点实验室知识库

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.

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.