Effects of N-Methyl-D-aspartate receptor (NMDAR) and Ca2+/ calmodulin-dependent protein kinase IIα (CaMKIIα) on learning and memory impairment in depressed rats with different charge by modified electroconvulsive shock

Abstract

Background: With the development of modified electroshock therapy (MECT), it has become necessary to increase the electric quantity in order to achieve a good antidepressant effect, but this increase will lead to more serious learning and memory impairment. The purpose of this study was to investigate the intrinsic mechanism of cognitive impairment induced by high-energy electroconvulsive shock (MECS, an animal model of MECT). Methods: Rats were randomly divided into 6 groups: control (C, n=6), M0, M60, M120, M180, and M240 groups (MECS at 0, 60, 120, 180, and 240 mC stimulation intensity after 80 mg/kg propofol, with 12 rats in each group). Their depression-like behavior and learning and memory ability were evaluated by sucrose preference test (SPT), open field test (OFT), and Morris water maze test (MWM). The expression of phospho-NMDA receptor 1 (GluN1), GluN2A, GluN2B, Ca 2+ /calmodulin-dependent protein kinase IIα (CaMKIIα), p-T305-CaMKII, and postsynaptic densities-95 (PSD-95) in hippocampus were detected by western blot. The co-expression of CaMKIIα and GluN2B subunit was detected by co-immunoprecipitation (CO-IP).Results: The chronic unpredictable mild stresses (CUMS) procedure successfully induced depression-like behavior in rats, which was improved in varying degrees after MECS. The results showed that the expression of GluN1, GluN2A, GluN2B, and PSD-95 decreased with the increase of charge, while p-T305-CaMKII increased, which led to the deterioration of learning and memory ability, but the expression change of CaMKIIα was not statistically significant.Conclusions: Increase in the MECS charge adjusts the synaptic plasticity by changing the binding amount of CaMKIIα and its subunit GluN2B and the level of CaMKII autophosphorylation, thereby impairing learning and memory functions.

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“…Briefly, sucrose solution (2%) and the drinking water were put in a cage for 6 hours. Finally, measure the liquid content and use the following formula to calculate the sucrose preference as previously described [ 17 ].…”

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