Abstract
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 (NCALD) 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 NCALD 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 NCALD silenced, then we overexpressed NCALD using adeno-associated virus. We also measured the protein levels of sGCα1, sGCβ1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA. Results Treating CUMS rats by silencing NCALD 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. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Limitation. We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied. Conclusions Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration.
Highlights
As a concerning disorder, depression decreased the quality of human life for its symptoms such as depressed mood and anhedonia. e World Health Organization ranks depression as a major cause of disabilities
Regarding the Forced Swimming Test (FST) (Figure 4(b)), we found that the rat immobility times for the chronic unpredictable mild stress (CUMS) + SAL and CUMS + associated virus (AAV) groups were longer than that of the CON + SAL group (P < 0.001), and the immobility time subsequently decreased after neurocalcin delta (NCALD) silencing (P < 0.01)
There have been a large number of preclinical data that indicate that AAV is viable as a carrier to treat central nervous system (CNS) diseases
Summary
Depression decreased the quality of human life for its symptoms such as depressed mood and anhedonia. e World Health Organization ranks depression as a major cause of disabilities (accounting for 7.5% of all persons with disabilities in 2015). 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 (NCALD) in chronic unpredictable mild stress (CUMS) rats. E aim of this study was, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing NCALD and using rescue experiments. Treating CUMS rats by silencing NCALD or by the administration of helicid improved the depressive-like behavior. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration
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