Effects Of Homer1a Mediated Esketamine On Learning And Memory Impairment Induced By Sleep Deprivation In Rats

Objective: To investigate the effects of low-dose esketamine on spatial learning and memory ability and the expression of Homer1 a,mGluR5 and AMPAR in hippocampus after chronic sleep deprivation.Methods: We selected 40 healthy Sprague-Dawley(SD)male rats aged 4 months,weighed200-280 g.They were divided into 4 groups randomly(n=10): Control group(N group),Sleep deprivation group(SD group),Sleep deprivation + Esketamine group(SDK group)and Sleep deprivation + Esketamine +AMPAR inhibitor group(SDKI group).Group N does nothing.The sleep deprived rats used the multi-platform water environment method to take sleep 24d(20 h/d);After that,group N and SD were intraperitoneally injected with the same dose of saline for three days,and SDK group was intraperitoneally injected with a small dose of Esketamine 10mg/kg.SDKI group was intraperitoneally injected with AMPAR inhibitor CNQX 1 mg/kg and low-dose Esketamine 10mg/kg.The spatial learning and memory ability of the rats was detected by Morris Water maze system.After the behavioral test was completed,all the four groups were injected intraperitoneally with 2-2-2-tribromoethanol(250mg/kg),and the rats were anesthetized and then sacrificed for sampling.The expression level of Homer1 a gene in hippocampus was detected by q PCR.The protein expressions of Homer1 a,mGluR5 and AMPAR in hippocampus were detected by Western blotting.The density of hippocampal neuronal dendritic spines was observed by Golgi staining.SPSS 25.0software was used for repeated measurement data variance analysis and one-way analysis of variance.Results: Compared with N group,the escape latency time of rats in SD group was prolonged,the percentage of residence time in target quadrant and the number of crossing platforms were decreased(P< 0.05),Homer1 a m RNA relative expression level increased(P< 0.05),Homer1 a and mGluR5 protein expression levels increased(P< 0.05),and AMPAR protein expression levels decreased(P< 0.05),the number of dendritic spines in hippocampal CA1 neurons were decreased(P< 0.05);After low dose of Esketamine,compared with SD group,the escape latency time of SDK group was shortened,the percentage of residence time in target quadrant and the number of crossing platforms were increased(P< 0.05),with AMPAR protein expression significantly up-regulated(P< 0.05),and no significant changes were observed in Homer1 a and mGluR5 expression(P> 0.05);Compared with the SDK group,the antagonist CNQX prolonged the escape latency time,decreased the percentage of residence time in the target quadrant and decreased the number of crossing platforms,which reversed the improvement effect of Esketamine on spatial learning and memory(P< 0.05)and significantly down-regulated the expression of AMPAR protein(P< 0.05).Conclusions: 1.24 days of chronic sleep deprivation can impair the learning and memory of rats,and low dose of Esketamine can alleviate the impairment.2.Sleep deprivation can induce the expression of Homer1 a,and regulate the expression of glutamate receptors mGluR5 and AMPAR in hippocampus thus impair the learning and memory ability of the rats.3.Low doses of Esketamine can improve learning and memory decline caused by sleep deprivation by increasing the expression of postsynaptic membrane AMPAR receptor.