Hyperforin alleviates the psychiatric disorders of adult rats suffered from early maternal separation via activating autophagy

Abstract

Rodent animals exposed to early maternal separation (EMS) show abnormal behaviors. Our previous study reported that autophagy is inhibited in the hippocampus of EMS rats, and hyperforin (HYP) alleviates depressive-like and anxious-like behaviors induced by EMS. However, the underlying mechanism of HYP is still unclear. In this study, we tested whether HYP alleviates the psychiatric disorders of EMS rats via activating autophagy. Pups were randomly divided into the control (CON) group, the EMS group, the EMS +3 mg/kg/day HYP (EMS + HYP) group and the EMS + treatment with 3 mg/kg/day fluoxetine (EMS + FT) group. Pups were separated from their mothers for 6 h every day from postnatal day 1 (PD1) to PD21 except pups of the CON group. Besides, HYP and FT were administered from PD22 to PD35 in the EMS + HYP group and the EMS + FT group respectively. Data showed that HYP not only reduced the level of glutamate, decreased the expression of N-methyl-d-aspartate receptor subunit 2B and postsynaptic density-95, but also increased the expression of synaptophysin of EMS rats. Interestingly, the expression of beclin-1 and the ratio of LC3II/LC3I were up-regulated in the EMS + HYP group. Moreover, HYP reduced the expression of the Notch1 receptor and the acetylation of H3K9 of EMS rats. In conclusion, our findings demonstrated that HYP ameliorates the depressive-like and anxious-like behaviors via activating autophagy in the hippocampus of EMS rats.