Development of a stable, early stage unilateral model of Parkinson's disease in middle-aged rhesus monkeys

Feng Ding, Liming Luan, Yi Ai, Ashley Walton, Greg A. Gerhardt, Don M. Gash, Richard Grondin, Zhiming Zhang

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

An important issue raised in testing new neuroprotective/restorative treatments for Parkinson's disease (PD) is the optimal stage in the disease process to initiate therapy. Current palliative treatments are effective in the early disease stages raising ethical concerns about substituting an experimental treatment for a proven therapy. Thus, we have endeavored to create a stable 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) nonhuman primate model of early PD. The new model was created by controlling for dose and route administration of MPTP (unilateral intracarotid infusion), and age of the animals (middleaged, 16-19 years old) in 27 female rhesus monkeys. All animals showed stable parkinsonian features lasting for up to 12-month as per behavioral evaluation. Compared with late-stage PD animals, postmortem analysis demonstrated that more dopaminergic neurons remained in the substantia nigra pars compacta, and more fibers were found in the striatum. In addition, tissue levels of striatal dopamine and its metabolites were also higher. Our results support that a milder but stable PD model can be produced in middle-aged rhesus monkeys.

Original languageEnglish
Pages (from-to)431-439
Number of pages9
JournalExperimental Neurology
Volume212
Issue number2
DOIs
StatePublished - Aug 2008

Bibliographical note

Funding Information:
This study was supported by USPHS NIH grants NS39787, AG013494 and NS050242.

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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