Objective To investigate the mechanism of Modified Shuyu Pills(MSP)in alleviating anxiety and depression behaviors in vascular dementia(VaD)mice.Methods For the pharmacological study,60 C57BL/6 mice were utilized to e...Objective To investigate the mechanism of Modified Shuyu Pills(MSP)in alleviating anxiety and depression behaviors in vascular dementia(VaD)mice.Methods For the pharmacological study,60 C57BL/6 mice were utilized to establish the VaD model through common carotid artery constriction/restraint stress(BCAS/CRS),with a sham operation serving as the control.Based on intervention conditions,the mice were divided into the control group(normal saline),model group(normal saline),MSP group(7,14,28 g·kg^(-1)),and fluoxetine group(10 mg·kg^(-1)).For the mechanism study,40 BCAS/CRS mice were treated with empty virus,MyRF overexpression virus,MSP(14 g·kg^(-1)),and MSP+MyRF knockdown virus,respectively.Behavioral changes were evaluated using the open-field test,elevated plus maze test,and tail suspension test.Western Blot analysis was employed to detect the expression of myelin-associated glycoprotein(MAG),myelin oligodendrocyteglycoprotein(MOG),myelin-basic protein(MBP)andmyelin-generegulatoryfactors(MyRF).MBP expression was also assessed through immunofluorescence staining.Compound action potential recordings in.the corpus callosum were conducted to evaluate the conductive efficacy of action potential in myelinated axons.Results Compared with the control group,the number/time of opening arms and the time/distance of the central area in the model groupwere significantly decreased,and the immobility time was prolonged(P<0.01).Expressions of MAG,MOG,MBP,and MyRF in mPFC and BLA were reduced,along with decreased MBP fluorescence intensity and action potential N1 amplitude(P<0.01).MSP and fluoxetine significantly increased the number/time of opening arms and the time/distance of the centra1l area,while shortening the immobility time(P<0.01,P<0.05).MSP and fluoxetine induced upregulation of myelin associated protein and MyRFexpression,as well as changes in MBP fluorescence intensity and action potential N1 amplitude(P<0.01,P<0.05).MyRF knockdown attenuated the improvement effect of MSP on the behavior,myelin-related protein expression,and action potential N1 amplitude of the model mice(P<0.01,P<0.05).Conclusion MSP ameliorates anxiety and depression behaviors in VaD mice by up-regulating the expression of MyRF and promoting myelin repair and signal transduction in the mPFC-BLA circuit.展开更多
文摘Objective To investigate the mechanism of Modified Shuyu Pills(MSP)in alleviating anxiety and depression behaviors in vascular dementia(VaD)mice.Methods For the pharmacological study,60 C57BL/6 mice were utilized to establish the VaD model through common carotid artery constriction/restraint stress(BCAS/CRS),with a sham operation serving as the control.Based on intervention conditions,the mice were divided into the control group(normal saline),model group(normal saline),MSP group(7,14,28 g·kg^(-1)),and fluoxetine group(10 mg·kg^(-1)).For the mechanism study,40 BCAS/CRS mice were treated with empty virus,MyRF overexpression virus,MSP(14 g·kg^(-1)),and MSP+MyRF knockdown virus,respectively.Behavioral changes were evaluated using the open-field test,elevated plus maze test,and tail suspension test.Western Blot analysis was employed to detect the expression of myelin-associated glycoprotein(MAG),myelin oligodendrocyteglycoprotein(MOG),myelin-basic protein(MBP)andmyelin-generegulatoryfactors(MyRF).MBP expression was also assessed through immunofluorescence staining.Compound action potential recordings in.the corpus callosum were conducted to evaluate the conductive efficacy of action potential in myelinated axons.Results Compared with the control group,the number/time of opening arms and the time/distance of the central area in the model groupwere significantly decreased,and the immobility time was prolonged(P<0.01).Expressions of MAG,MOG,MBP,and MyRF in mPFC and BLA were reduced,along with decreased MBP fluorescence intensity and action potential N1 amplitude(P<0.01).MSP and fluoxetine significantly increased the number/time of opening arms and the time/distance of the centra1l area,while shortening the immobility time(P<0.01,P<0.05).MSP and fluoxetine induced upregulation of myelin associated protein and MyRFexpression,as well as changes in MBP fluorescence intensity and action potential N1 amplitude(P<0.01,P<0.05).MyRF knockdown attenuated the improvement effect of MSP on the behavior,myelin-related protein expression,and action potential N1 amplitude of the model mice(P<0.01,P<0.05).Conclusion MSP ameliorates anxiety and depression behaviors in VaD mice by up-regulating the expression of MyRF and promoting myelin repair and signal transduction in the mPFC-BLA circuit.
