Corticolimbic analysis of microRNAs and protein expressions in scopolamine-induced memory loss under stress.

The aim of the present study was to assess thealterations of corticolimbic microRNAs and protein expressions in the effect of scopolamine with or without stress on passive-avoidance memory in male Wistar rats. The expressions of miR-1, miR-10 and miR-26 and also the levels of p-CREB, CREB, C-FOS and BDNF in the prefrontal cortex (PFC), the hippocampus and the amygdala were evaluated using RT-qPCR and Western blotting techniques. The data showed that the administration of a muscarinic receptor antagonist, scopolamine or the exposure to 30 min stress significantly induced memory loss. Interestingly, the injection of an ineffective dose of scopolamine (0.5 mg/kg) alongside with exposure to an ineffective time of stress (10 min) impaired memory formation, suggesting a potentiative effect of stress on scopolamine response. Our results showed that memory formation was associated with the down-regulated expression of miR-1, miR-10 and miR-26 in the PFC and the hippocampus, but not the amygdala. The relative expression increase of miR-1 and miR-10 in the PFC and the hippocampus was shown in memory loss induced by scopolamine administration or 30-min stress. The PFC level of miR-10 and also hippocampal level of miR-1 and miR-10 were significantly up-regulated, while amygdala miR-1 and miR-26 were down-regulated in scopolamine-induced memory loss under stress. Memory formation increased BDNF, C-FOS and p-CREB/CREB in the PFC, the hippocampus and the amygdala. In contrast, the PFC, hippocampal and amygdala protein expressions were significantly decreased in memory loss induced by scopolamine administration (2 mg/kg), stress exposure (for 30 min) or scopolamine (0.5 mg/kg) plus stress (10 min). One of the most significant findings to emerge from this study is that the stress exposure potentiated the amnesic effect of scopolamine may via affecting the expressions of miRs and proteins in the PFC, the hippocampus and the amygdala. It is possible to hypothesis that corticolimbic signaling pathways play a critical role in relationship between stress and Alzheimer's disease.