Through the application of behavioral and molecular imaging methods to dynamically assess the clinical characteristics of the cynomolgus monkey Parkinson's disease systemic model, provide a stable and effective PD for preclinical studies of drugs, stem cells and other therapies and provide a primate model.
Method 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1-methyl-4-phenyl-1,2), 3 times in a row to 7 healthy eating crabs between 10 and 15 years old Monkey injected intravenously. ,6-Tetrahydropyridine, MPTP) 0.2mg/kg body weight, induce a systemic PD model, continue to observe the progression of PD symptoms for 3 months, and then intervene with levodopa. The PD score scale is used to assess the severity of animal clinical symptoms, the EtheVision animal motion track tracking system is used to analyze random travel distance and track changes, and positron emission tomography (positron emission tomography, PET) uses molecular imaging agents "F -AV-133 assesses the functional status of dopaminergic neurons in the striatum.
All animals shivered and their muscles were stiff 14 days after MPTP injection. The clinical score reached a peak at 1 month (21.43 ± 5.35), after which the PD symptoms were stable, and the observation was continued for 2 months (18.43 ± 3.87) and 3 months (18.14) ± 3.53, and at the end of MPTP injection (14.43 ± 1.90) In comparison, the clinical scores were significantly improved (Pu003c0.05). Spontaneous movement distance (809.77 ±). 401.15 cm was significantly shorter than the baseline (8627.46 ± 5751.04) cm (Pu003c0.01) at 3 months. \"F-AV-133 The average specific uptake rate (Sur) of the bilateral striatum at 3 months (0.16±0.03) was significantly lower than the baseline (1.66±0.58) (Pu003c0.01). Levodopa After the intervention, PD symptoms were significantly improved, the clinical score (12.86±3.63) was significantly lower than the model period (Pu003c0.05), and the voluntary walking distance was significantly increased (P. u003c0.05). ).
Conclusion The clinical manifestations of the whole body model of PD cynomolgus monkey constructed in this study remain stable. Striatal dopaminergic nerve injury is effective for levodopa intervention, and there is no self-healing during the whole process. The clinical characteristics of simulated PD dynamics are expected to provide an experimental basis for future PD research.