Helicid Reverses the Effect of Overexpressing , Which Blocks the sGC/cGMP/PKG Signaling Pathway in the CUMS-Induced Rat Model.

BACKGROUND

Increasing evidence has shown that apoptosis in the hippocampus is closely related to depressive-like behavior. We previously reported that helicid had good antidepressant activities, which manifested as the alleviation of depression-like behaviors and the reversal of the high expression of neurocalcin delta () in chronic unpredictable mild stress (CUMS) rats. The aim of this study was, therefore, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing and using rescue experiments.

METHODS

We developed the CUMS rat model using CUMS stimulation from week 0 to week 6. The rats were treated with helicid, or silenced, then we overexpressed using adeno-associated virus. We also measured the protein levels of sGC1, sGC1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA.

RESULTS

Treating CUMS rats by silencing or by the administration of helicid improved the depressive-like behavior. The levels of proteins, including sGC, PKG, cleaved caspase-3, and cGMP, in hippocampus all decreased. overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. . We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied.

CONCLUSIONS

Inhibition of , as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing reversed the amelioration effects of silenced and helicid administration.