Helicid alleviates depression-like behavior in rats with chronic unpredictable mild stress through the NCALD/sGC/cGMP/PKG axis
DU Xin
ZHANG Xiaotong
LU Juan
GE Peng
HU Haitao
FU Mengxue
ZHANG Yuanxiang
WANG Guodong
TONG Jiucui
Abstract：Objective To investigate the molecular mechanism of helicid for improving depressive-like behaviors in rats exposed to chronic unpredictable mild stress(CUMS).Methods SD rats were randomly divided into normal control group(n=20)and CUMS group(n=70)to receive no stimulation and mild unpredictable stress for 6 weeks,respectively.After successful modeling,CUMS rats were further divided into 7 subgroups for intracerebroventricular injection with saline,adeno-associated virus(AAV)vector,or AAV carrying si-NCALD(NCALD silencing experiment,n=10);or intracerebroventricular injection with saline,saline with daily helicid gavage,AAV vector with helicid gavage,or NCALD-overexpressing AAV with helicid gavage(NCALD overexpresison experiment,n=10).The depressive state of the rats was evaluated by assessing changes in body weight,sucrose preference,and open field test.The expressions of NCALD,sGCα1,sGCβ1,PKG1/2,and cleaved-caspase 3 in the hippocampus of the rats were detected by Western blotting,and hippocampal cGMP level was determined with ELISA.Results Compared with the normal control rats,CUMS rats showed significantly increased hippocampal expressions of NCALD and cleaved caspase-3 and abnormal activation of the sGC/cGMP/PKG pathway.Silencing NCALD by intracerebroventricular injection of AAV-si-NCALD significantly reduced cleaved caspase-3 and inhibited sGC/cGMP/PKG pathway activation in the hippocampus,and improved depressive-like behaviors of the rats.Helicid treatment produced similar effects,but its effect was abolished by intracerebroventricular injection of NCALD-overex-pressing AAV.Conclusion Helicid relieves depressive-like behaviors in CUMS rats by downregulating NCALD,inhibiting abnormal sGC/cGMP/PKG activation,and reducing hippocampal apoptosis.
Keywords：helicidneurocalcin δsGC/cGMP/PKG signaling pathwaychronic mild unpredictable stress
Publication Date：2025-12-20
Online Publishing Date：2025-12-31(First online date of this platform, not the publication date of the document)
Pages：9( 2699-2707 )