| Purpose;To establish a modeling method that is not only safe to operate but also can simulate the clinical symptoms and pathological process of Parkinson’s Disease(PD).METHODS:Three healthy male cynomolgus monkeys were selected and administered with Alzet osmotic pressure sustained release technology to release MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced dose of 0.2 mg/kg/day).Before and after the experiment,the Primate Scan primate intelligent fine behavior analysis system was used for 1h recording under standard environmental conditions,and the behavioral changes of monkeys were scored by using the Kurlan Scale,which can be used to evaluate the dyskinesia severity of monkeys.Positron Emission Tomography(PET)was performed 1 month after successful modeling to confirm whether the experimental cynomolgus monkeys met the criteria for successful imaging modeling.At the end of the experiment,"all animals were sacrificed",and morphological changes of dopaminergic neurons in the substantia nigra and striatum were detected by murine tyrosine hydroxylase antibody.RESULTS:All three cynomolgus monkeys were successfully modeled.Modeled monkeys showed typical Parkinson’s disease-like symptoms such as bradykinesia,increased muscle tone,limb tremor,and behavioral scores of them were more than 29 points.SPE imaging was obtained by positron emission tomography with 18F-dopa as a tracer.The radioactive uptake in the bilateral striatum of the cynomolgus monkeys was reduced,and the distribution on both sides was uneven.Immunohistochemistry showed that the number of TH-positive neurons in the model monkeys was significantly reduced,and the residual neurons were degenerated.RESULTS:Alzet osmotic pressure sustained-release technology sustained-release MPTP method can establish a good model to simulate the clinical symptoms and pathological process of PD patients.It is a reliable experimental animal model for studying the etiology,pathogenesis,drug therapy and gene therapy of PD. |
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