کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3055527 1580176 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modeling Parkinson's disease in monkeys for translational studies, a critical analysis
ترجمه فارسی عنوان
مدل سازی بیماری پارکینسون در میمون ها برای مطالعات ترجمه، یک تجزیه و تحلیل بحرانی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
چکیده انگلیسی


• We review records of 108 MPTP treated macaques.
• We analyze parameters of MPTP treatment in relation to model outcomes.
• Stable parkinsonian models require individual adjustment of MPTP treatment.
• L-DOPA induced dyskinesia depends on the degree of parkinsonism.
• We provide guidelines for systemic MPTP treatment in macaques.

The non-human primate MPTP model of Parkinson's disease is an essential tool for translational studies. However, the currently used methodologies to produce parkinsonian monkeys do not follow unified criteria, and the applied models may often fall short of reproducing the characteristics of patients in clinical trials. Pooling of data from the parkinsonian monkeys produced in our Centers provided the opportunity to evaluate thoroughly the behavioral outcomes that may be considered for appropriate modeling in preclinical studies. We reviewed records from 108 macaques including rhesus and cynomolgus species used to model moderate to advanced parkinsonism with systemic MPTP treatment. The attained motor disability and the development of levodopa-induced dyskinesias, as primary outcomes, and the occurrence of clinical complications and instability of symptoms were all analyzed for correlations with the parameters of MPTP administration and for estimation of sample sizes. Results showed that frequently the MPTP-treated macaque can recapitulate the phenotype of patients entering clinical trials, but to produce this model consistently it is important to adapt the MPTP exposure tightly according to individual animal responses. For studies of reduced animal numbers it is also important to produce stable models, and stability of parkinsonism in macaques critically depends on reaching “marked” motor disability. The analyzed data also led to put forward recommendations for successfully producing the primate MPTP model of Parkinson's disease for translational studies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 256, June 2014, Pages 133–143
نویسندگان
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