Improvement Of Symptoms And Histological Effects Of Polydopamine Nanoparticles On MPTP-induced PD Mice Model

Objective:Parkinson’s disease（PD）is a common degenerative disease of the aged nervous system,its incidence is increasing with the aging of society,which is a burden to individuals,society and the country The main pathological change of PD was significant degeneration and death of dopaminergic（DA）neurons in the substantia nigra and striatum region of the midbrain.abnormal aggregation of α-synuclein in the Lewy’s body is a significant marker of the pathological changes of PD.The pathogenesis of PD is still unclear.Polydopamine nanoparticels（PDA NPs）are fully organic 、 biodegradable and biocompatible nanostructures,which have been shown to have excellent antioxidant capacity and suppress abnormal aggregation of α-synuclein in the nerve cells.our experiment aims to study the improvement effect and histological effect of polydopamine nanoparticles on MPTP mouse model of Parkinson’s disease.Methods:In this study,18 adult male C57BL/6N mice were randomly divided into three groups:the control group（Na Cl group）,the model group（MPTP group）and the experimental group（MPTP+ PDA NPs）).Subacute MPTP Parkinson’s disease mouse model was established（MPTP was intraperitoneally injected at 30mg/kg weight once a day for 5 consecutive days）.First,the above dose of MPTP was administered,followed by an experimental dose of PDA NPs injected intraperitoneally for treatment（PDA NPs was intraperitoneally injected at 7.5mg/kg weight once a day for 2 weeks）.The pathological influence of organs（heart,liver,kidney,lung and spleen）of PDA NPs group were observed by HE staining and assessed the impact on the mice by monitoring body weight changes in the three groups.The quantity、distribution and morphology of tyrosine hydroxylase positive cells in the substantia nigra and striatum of mouse brain were detected by immunohistochemistry and HE staining.The motor ability and limb muscle strength of mice were evaluated by traction test、 pole test、field test、and swimming test.Western blot was used to detect the expression levels of TH and α-synuclein in the substantia nigra and striatum of mice.Results:（1）The results of body weight and HE staining showed that there was no significant change between three groups;Compared with the control group,no obvious biological toxicity was observed on mice of PDA NPs group.（2）The results of traction test showed that compared with the control group,the mice of model group reduced the strength of fore and hind limbs,and the strength of fore and hind limbs of mice were improved after treatment with PDA NPs;the results of field test showed that compared with the control group,the mice of model group reduced the ability of spontaneous and exploratory behavior,the ability of spontaneous and exploratory behavior were improved after treatment with PDA NPs;the results of pole test showed that compared with the control group,the mice of model group increased the time for the mice to move from the top of the pole to the bottom,while there was no significant change between the model group and PDA NPs group;the results of swimming test showed that compared with the control group,the mice of model group increased the swimming time,while there was no significant change between the model group and PDA NPs group.These results indicated that coordination ability of the mice was improved after PDA NPs treatment.（3）The results of HE staining and immunohistochemistry showed that compared with the control group,the number of TH positive cells in substantia nigra and the number of nerve fiber in striatum in model group and PDA NPs group decreased.（4）The results of Western blot showed that the expression level of TH protein in substantia nigra and striatum decreased and the expression level of α-synuclein protein in substantia nigra and striatum increased,After the model mice were treated with PDA NPs,the above phenomenon was inhibited.Conclusion:（1）PDA NPs has no obvious biological toxicity in mice.（2）PDA NPs improved the movement disorders of MPTP-induced PD mice model.（3）PDA NPs inhibited the level of α-synuclein in substantia nigra and striatum region of the Parkinson’s disease mice model,and restore the level of TH in substantia nigra and striatum region of the Parkinson’s disease mice model.