The Mechanism Of Yueju Pill To Improve Depression With Cognitive Defieit

Depression is characterized by depression,pessimism,sleep disorders,and severe cases are often accompanied by suicidal thoughts or behaviors.The stud y by the World Health Organization in conjunction with the China Association for the Prevention and Control of Mental Diseases shows that the number of p eople suffering from depression in China exceeds 61 million,becoming the sec ond most serious disease burden of the national disease,with extremely high d isabling and fatal,which seriously endangers the national health.And most dep ression patients suffer from severe cognitive deficits including executive functio n,memory and attention deficit.However,due to the complexity of the diseas e,so far its pathogenesis is still unknown.At present,the limitations and side effects of first-line western medicine are very prominent.Chinese traditional m edicine Yueju pills(YJ)from the "Danxi Heart Law",has the effect of regula ting qi and relieving depression,but its application to depression with cognitive injury treatment research reports less.Objective:To investigate the effect of Yueju Pill on the improvement of depression with cognitive injury in mice and the molecular biology and neurobiological m echanism.METHODS:1.By comparing the efficacy of Yueju pills in different strains of mice,the mechanism of treatment of depression was determined.2.Using C57BL/6J mice to explore the effect of Yueju Pill on the impro vement of depression with cognitive injury in corticosterone model animals,an d to explore the deep mechanism of Yueju Pill to improve depression with cog nitive injury from the mechanism of enhancing neural plasticity in PKA-CREB-BDNF pathway.RESULTS:1.Behavioural studies have shown that Yueju pills can act on Balb/c mice and have no effect on C57BL/6J mice.Based on this,we studied the molecula r mechanism of Yueju Pill acting on the difference between two mouse lines.Studies on the hippocampus of depression-related brain regions in mice found t hat Balb/c mice up-regulated the expression of PKA-CREB-BDNF under the ac tion of Yueju Pill,while C57BL/6J mice did not change.The electrophysiologi cal results showed that Balb/c mice showed increased long-term enhancement(LTP)under the action of Yueju Pill,but C57BL/6J mice could not increase L TP..to verify the relationship between the PKA-CREB pathway and the antide pressant mechanism in mice,we H-89 preadministered by PKA blockers,and t he antidepressant effect of yuju pill was blocked in the suspension test after 30 min.But the antidepressant effect of ketamine was not blocked in the suspe nsion test,but in forced swimming two hours later it was blocked.Next,the PKA-CREB pathway was activated by first gavage and then intraperitoneal inje ction after 3 h.The results showed that the immobility time of Yueju pills in suspension and forced swimming test had no significant change compared with that in control group,but ketamine had significant effect in both suspension an d forced swimming test.2.In the corticosterone model,Yueju pills can improve depression-like sy mptoms after two weeks of administration compared with Escitalopram.In the water maze test,Yueju pills can shorten the incubation time of mice on stage.At the same time,Yueju pills can increase the neurogenesis level(Ki67)in h ippocampus of mice.after 4 weeks of administration,both yuju pill and escital opram could reverse depressive-like behavior and shorten the stage incubation p eriod,increase platform crossing times,increase the ratio of mouse in target qu adrant time to total time,increase the ratio of mouse time to total time in nov el arm,and increase the ratio of mouse distance to total distance in new arm.up-regulated PKA-CREB-BDNF pathway expression and increased dendritic spin e density in CA1 region.These effects can be reversed by the administration o f neuroplastic blockers.CONCLUSION1.Yueju pills have different antidepressant effects in different strain mice and rely on PKA-CREB signaling pathways to produce antidepressant effects in Balb/c mice.2.Yueju pills rely on PKA-CREB pathway to increase neuroplasticity to i mprove depression with cognitive impairment.At the same time,compared wit h western medicine,Yueju pills improve faster than that of western medicine.