Research On The Early Pathological Mechanism Of Inositol Hexaphosphate In Parkinson's Disease

Objective:To investigate the effect of inositol hexaphosphate?IP₆?in preventing Parkinson's disease of C57BL/6 mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine?MPTP?,on the expression of tyrosine hydroxylase?TH?in the substantia nigrasynaptic,the changes of synaptic vesicle circulation and synaptic structure,the expression of dopamine transporter?DAT?and synapse associated protein 25?SNAP-25?,then study the mechanism of IP₆ on synaptic dysfunction in PD model.Methods:C57BL/6 mice were divided into control group,MPTP group and IP₆ group.Detection the movement coordination function by the rotarod apparatus.The expression of tyrosine hydroxylase?TH?was detected by immunofluorescence in substantia nigrasynaptic.Scanning technique of transmission electron microscope was used to observe the synaptic vesicle cycle and changes in the structure.Immunofluorescence was used to detect the expression of DAT and SNAP-25.The content of DAT and SNAP-25 were analyzed by western blotting.Results:1.Compared with control group,the motor ability of mice in MPTP group was decreased?P<0.01?,IP₆ could improve motor dysfuntion in contrast with MPTP group?P<0.05?.2.By TH detection,the activity of TH was decreased,dopaminergic cells were reduced in the PD model.IP₆ could reduce the reduction of dopaminergic cells and relieve this symptom.3.Compared with the Control group,the synaptic circulation in the substantia nigra was disturbed and the vesicles were obviously damaged in the Control group,while the release of synaptic vesicles in the IP6 group was changed.IP₆ could inhibit the changes of the early vesicle injury disorder induced by MPTP.4.The expression of DAT/SNAP-25decreased in MPTP group by immunofluorescence detection,compared with the MPTP group,the expression of DAT/SNAP-25 increased in IP₆ group.IP₆ can increased the expression of DAT/SNAP-25 in PD model.5.In relation to Control group,the expression of DAT/SNAP-25in PD model group was significantly decreased by Western blot?P<0.01?.Compared with MPTP group,the expression of DAT/SNAP-25 in MPTP group was increased?P<0.05?.IP₆could improve the expression of vesicular circulatory associated protein.Conclusion:IP₆ plays an important role in the early pathological changes of MPTP induced PD mice model,which may be associated with the expression of synaptic vesicle cycle and related regulatory factors DAT and SNAP-25 in substantia nigra striatum of mice.IP₆ could prevent dopaminergic neuron injury and improve Parkinson's symptoms by the behavioral observation and TH activity test.Electron microscopy showed that IP₆ inhibited early synaptic vesicle circulation disorder in MPTP induced PD mice model.The results of tissue immunofluorescence and western blot showed that IP₆ could increase the expression of DAT and SNAP-25.The intention of this test was to establish PD mice model,further study the related mechanisms,which may be provide new strategies for early diagnosis and treatment of PD.