Effect Of Long-term Enrichment Environment On Depression In PD Model Mice Induced By Neurotoxin MPTP

BackgroundAn enriched environment is a living environment that enhances happiness,motor ability,and cognitive performance,and has been shown to play a positive role in many diseases,such as Alzheimer’s disease,post-stroke rehabilitation,anxiety,depression,and neuropathic pain.Research on Parkinson’s disease-related depression has attracted more and more attention from scholars.The treatment methods are divided into drug therapy and non-drug therapy,electroconvulsive therapy(ECT),cognitive behavioral therapy(CBT),and deep brain stimulation(DBS)have been widely used in clinical practice,especially suitable for patients with depression who have developed drug-resistant PD.There are no reports of abundant environment and Parkinson-related depression.ObjectiveTo investigate the effect of long-term enriched environment on depression in PD model mice induced by neurotoxin MPTP.MethodsForty 7-month-old male C57BL/6N mice were randomly divided into EE+MPTP group,EE+NS group,SE+MPTP group and SE+NS group,with 10 mice in each group.After 3 months of intervention in the EE group,mice in the MPTP group were given neurotoxin MPTP model(intraperitoneal injection,30mg/kg)once a day for consecutive 7days,and the NS group was given the same amount of 0.9%Na Cl intraperitoneal injection as control.After the modeling,we began the behavioral experiment and measured the body weight growth rate of the mice,to observe and evaluate the behavioral performance and body weight changes of the mice.After the behavioral experiment,the whole brain of the mice was collected and immunohistochemical staining of TH and 5-HT1 A receptor was performed.Image-Pro Plus 6.0 software was used to analyze the surface density value(IOD/AREA),and the higher the value,the higher the positive expression level.Statistical analysis was performed using SPSS 26.0 version.The data were subjected to normal distribution test and homogeneity of variance test before analysis.The measurement data of normal distribution were described as mean standard deviation.The one-way analysis of variance(ANOVA)was used to compare the measurement data among multiple groups and between two groups,and P<0.05 indicated that the difference was statistically significant.Results1.Growth rate of body weight: Compared with the NS group,the body weight growth rates of the EE+MPTP group and the SE+MPTP group were decreased(both P<0.05).However,the reduction in the score of EE+MPTP group was milder than that of SE+MPTP group,and the reduction was statistically significant(P<0.05)。2.Pole test:Compared with the NS group,the test scores of the EE+MPTP group and the SE+MPTP group were both significantly reduced(both P<0.01).However,the reduction in the score of the EE+MPTP group was less significant than that of the SE+MPTP group(P<0.05).3.Sucrose preference test:Compared with the NS group,the sucrose preference in the EE+MPTP group and the SE+MPTP group were significantly reduced(both P<0.01).Compared with the SE+MPTP group,the sucrose preference in the EE+MPTP group was higher than that in the SE+MPTP group(P<0.01)4.Force-swimming test(FST):Compared with the NS group,the scores of the EE+MPTP group and the SE+MPTP group were significantly reduced(both P<0.01),and the reduction in the score of EE+MPTP group was milder than that of the SE+MPTP group(P<0.05).5.Tail suspension test(TST):Compared with the NS group,the quiescent time of mice in the EE+MPTP group and the SE+MPTP group was significantly increased(both P<0.01).However,compared with the SE+MPTP group,the mice in the EE+MPTP group exhibited more intense struggling against uncomfortable positions(P<0.05).6.TH immunohistochemical assay: Compared with the NS group,MPTP group had more obvious loss of damaged dopaminergic neurons,but more TH-positive cells were expressed in the EE+MPTP group than in the SE+MPTP group(P<0.05).7.Immunohistochemical determination of 5-HT1 A receptor: Significant loss of5-HT1 A receptors was observed in the MPTP group compared with the NS group,but more 5-HT1 A receptor-positive cells were expressed in the EE+MPTP group compared with the SE+MPTP group(P<0.01).Conclusion1.The neurotoxin MPTP can induce C57BL/6N mice to exhibit motor dysfunction and depressive states of Parkinson’s disease.2.Enriched environmental intervention can improve dyskinesia and alleviate the depressive state of PD mice.