Kaixin-San improves Aβ-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.

Automated summary

This study investigated the mechanism by which Kaixin-San (KXS) mitigates the toxic effects of amyloid-beta protein (Aβ) by regulating the expression of postsynaptic AMPA receptors (AMPARs). The results showed that KXS effectively improved the learning and memory impairment caused by Aβ, and reversed the inhibition of hippocampal long-term potentiation (LTP) induced by Aβ. The expression levels of several accessory proteins associated with AMPAR expression were also altered by KXS. These findings provide novel insights into the mechanism underlying the neuroprotective effects of KXS against Aβ-induced memory impairment.