Kaixin-San improves A beta-induced synaptic plasticity inhibition by affecting the expression of regulation proteins associated with postsynaptic AMPAR expression

Objective: To explore the mechanism underlying Kaixin-San (KXS) regulation of postsynaptic AMPA receptor (AMPAR) expression to mitigate toxic effects of the amyloid-beta protein (A beta).Methods: An animal model was established via intracerebroventricular injection of A beta 1-42. The Morris water maze test was conducted to evaluate learning and memory, while electrophysiological recording was conducted to assess the hippocampal long-term potentiation (LTP). Western blotting was used to detect expression levels of the hippocampal postsynaptic AMPAR and its accessory proteins.Results: The time spent to find the platform was significantly prolonged, the number of mice crossing the target site was significantly reduced, and the maintenance of LTP was inhibited in the A beta group than in the control group. In the A beta/KXS group, the time taken to find the platform was significantly shortened and the number of mice crossing the target site was significantly increased than in the A beta group; furthermore, the inhibition of LTP induced by A beta was reversed. The expression of GluR1, GluR2, ABP, GRIP1, NSF, and pGluR1-Ser845 was upregulated, while that of pGluR2-Ser880 and PKC delta was downregulated in the A beta/KXS group.Conclusion: The increased expression of ABP, GRIP1, NSF, and pGluR1-Ser845 and the decreased expression of pGluR2-Ser880 and PKC delta under the influence of KXS, followed by the upregulation of postsynaptic GluR1 and GluR2, alleviated the inhibition of LTP induced by A beta. Ultimately, the memory function of model animals was improved by KXS. Our study provides novel insights into the mechanism underlying KXS mitigation of A beta-induced synaptic plasticity inhibition and memory impairment by altering the levels of accessory proteins associated with AMPAR expression.