Twice Subacute MPTP Administrations Induced Time-dependent Dopaminergic Neurodegeneration And Inflammation In Midbrain And Ileum,as Well As Gut Microbiota Disorders In PD Mice

Objective: Parkinson's disease(PD)is a common progressive neurodegenerative disease.In PD,except a few cases with familial heritability,more than 90 % are sporadic,which are affected by internal and external environmental factors and have the characteristics of chronic progression.Immune and gut microbiota(GM)disorder exist in PD,but the pathological mechanism remains unexplored.PD produces a pathological state in the intestine and disordered GM,which may be important for the pathogenesis and progression of PD,but it is not clear.In order to understand the similarities and differences of brain and gut immune responses,changes in GM and gut injury under different pathological conditions of PD,we used neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)to simulate the environmental damage factors of PD.Methods: To explore the conditions and characteristics of intestinal pathology and GM disorders when PD-related injuries occur,we used twice MPTP subacute administration with an interval of 3 weeks(each was an intraperitoneal injection of 25 mg/kg MPTP for 5 consecutive days).We observed the changes in intestinal and brain immune status,intestinal barrier function and GM in different injury states one day,one week,and three weeks after the first stimulus and one day and one week after the second stimulus.Results: Our study found that two subacute administrations of MPTP induced dopaminergic neuron injury and inflammation in the midbrain and ileum,impaired intestinal barrier function and GM disorders closely related to administration.These changes recovered after the first administration,but after repeated administration,some indicators showed more dramatic changes than during the first administration.Conclusion: Our results suggest that the intestinal tract is sensitive to PD-related injury,and the GM is susceptible to disturbances caused by intestinal function,which may be concerned in local immune disorders of the intestine.