Effect of Yiqi Huatan decoction in inhibiting NLRP3 inflammasome on the modulation of synaptic dysfunction in depressed mice
Objective:To explore how Yiqi Huatan Decoction can modulate synaptic dysfunction in a mouse model of chronic unpredictable mild stress(CUMS)depression by suppressing NLRP3 inflammasome in microglia and A1-like astrocytes activa-tion.Methods:C57BL/6J mice were categorized into four groups:normal,model,MCC950,and Yiqi Huatan Decoction.With the exception of the normal group,all other groups underwent CUMS to induce depression,and subsequently received either MCC950 or Yiqi Huatan Decoction as treatment.The depression-like behavior of mice was evaluated using the Sucrose preference test(SPT),Novelty suppressed feeding test(NSF),Tail suspension test(TST),and Forced swimming test(FST).The syn-aptic structure of the hippocampus was examined through Golgi staining.Immunofluorescence staining was utilized to detect the co-localization of GFAP and C3,as well as Iba1 and NLRP3 in the hippocampus of mice.Additionally,the mRNA levels of TNF-α,IL-1α,and C1qA were measured using quantitative Real-time PCR.The protein expression of SYP,PSD-95,C3,NL-RP3,ASC,Caspase-1,and IL-1β in the mouse hippocampus were determined through Western Blot analysis.Results:Com-pared to the control group,the mice in the experimental group exhibited a notable decrease in sucrose preference,an extended peri-od of time before initiating feeding in NSF,and an increased duration of immobility in both TST and FST(P<0.05).In addition,mice exhibiting depressive symptoms demonstrated a reduction in the quantity of dendritic branches and dendritic spine density within the hippocampus(P<0.01).Furthermore,there was a notable rise in the number of co-localized positive cells expressing GFAP and C3 or Iba1 and NLRP3(P<0.01),along with elevated levels of TNF-α,IL-1α,and C1qA mRNA expression(P<0.01).Conversely,a decrease in the expression of SYP and PSD-95 proteins was observed(P<0.05),while a significant increase in the expression of C3,NLRP3,ASC,Caspase-1,and IL-1β proteins was noted(P<0.01).In contrast to the model group,the mice in the Yiqi Huatan Decoction group exhibited a higher sucrose preference rate and reduced latency in NSF.Additionally,the immobility time in both TST and FST was significantly decreased(P<0.01).Furthermore,the administration of Yiqi Huatan De-coction to mice resulted in a significant increase in the number of hippocampal dendritic branches and dendritic spine density(P<0.01).Additionally,there was a significant decrease in the number of co-localised positive cells of GFAP and C3,Iba1 and NL-RP3(P<0.01).Moreover,the mRNA levels of TNF-α,IL-1α,and C1qA were significantly reduced(P<0.01),while the pro-tein expression of SYP and PSD-95 increased(P<0.05).Conversely,the protein expression of C3,NLRP3,ASC,Caspase-1,and IL-1β were all significantly reduced(P<0.05).Conclusion:The administration of Yiqi Huatan Decoction has been found to mitigate synaptic function impairment and ameliorate depressive-like behavior in mice subjected to CUMS.This therapeutic effect is achieved through the inhibition of NLRP3 inflammasome activation in hippocampal microglia and the reduction in the activation of neurotoxic A1-like astrocytes.
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