Neuroprotective effects and mechanism of calycosin in a mouse model of post-stroke depression
SHAN Yonglin
ZHANG Zhiqian
LIU Xiaolong
WEI Wei
HAN Qinglin
SUN Kunkun
SHAN Yudong
Abstract:Objective To investigate the neuroprotective effect of calycosin(CA)on post-stroke depression(PSD)in mice and its potential association with NOD-like receptor protein 3(NLRP3).Methods A total of 60 SPF-grade male C57BL/6 mice(8 weeks old)were randomly divided into control,model,low-dose CA treatment(CA-L,20 mg/kg),high-dose CA treatment(CA-H,40 mg/kg),and high-dose CAplus NLRP3 agonist treatment(40 mg/kg CA+0.1 mg/kg nigericin)groups,with 12 animals in each group.A PSD model was established by transient middle cerebral artery occlusion(tMCAO)followed by chronic restraint stress(CRS).Tail suspension test(TST)and sucrose preference test(SPT)were used to assess depressive-like behaviors.HE staining was employed to observe the pathological changes,immunofluorescence assay was utilized to detect the NLRP3 expression in the basolateral amygdala(BLA),and ELISA was performed to measure the contents of IL-1β and IL-18 in BLA tissue.Results Compared with the model group,the CA-L and CA-H groups exhibited significantly increased sucrose preference,reduced immobility time in TST,downregulated NLRP3,and decreased IL-1β and IL-18 contents in the BLA.Co-administration of nigericin,NLRP3 agonist,resulted in increased cellular disorganization,degeneration,and necrosis,and lower sucrose preference[(82.25±4.77)%vs(65.46±5.04)%],longer immobility time(95.66±9.23 s vs 144.75±11.35 s),lower NLRP3 level(61.36±6.01 AU vs 105.26±6.31 AU),and decreased contents of IL-iβ(15.28±1.42 ng/mL vs 26.35±2.41 ng/mL),and IL-18(16.47±1.31 ng/mL vs 28.72±2.15 ng/mL)when compared with the CA-H group(P<0.05).Conclusion CA exerts significant neuroprotective effects in a mouse model of PSD,potentially due to its inhibiting NLRP3 inflammasome-mediated neuroinflammatory responses.
Keywords:calycosinneuroprotectionpost-stroke depressionNOD-like receptor thermal protein domain associated protein 3interleukins
Publication Date:2026-03-15
Online Publishing Date:2026-03-31(First online date of this platform, not the publication date of the document)
Pages:5( 388-392 )