Basal ganglia lesions after MPTP administration in rhesus monkeys

• Published in: Neurobiology of disease Vol. 23; no. 2; pp. 281 - 289
• Main Authors: Emborg, M.E., Moirano, J., Schafernak, K.T., Moirano, M., Evans, M., Konecny, T., Roitberg, B., Ambarish, P., Mangubat, E., Ma, Y., Eidelberg, D., Holden, J., Kordower, J.H., Leestma, J.E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2006; Elsevier
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Aging; Animals; Basal Ganglia - drug effects; Basal Ganglia - pathology; Female; Gene therapy; Genetic Therapy - methods; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - therapeutic use; Globus pallidus; Macaca mulatta; Male; MPTP; Necrosis; Neurotoxins; Nonhuman primates; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - pathology; Parkinsonian Disorders - therapy; Striatum; Stroke; Striatum; Stroke; Parkinson's disease; Nonhuman primates; Globus pallidus; Aging; MPTP; Gene therapy; Necrosis
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2006.03.010

In monkeys, intracarotid infusion of a single low dose of MPTP reliably induces a hemiparkinsonian syndrome that is stable over time. This model has been widely used to assess novel anti-parkinsonian therapies. Here, we report the exceptional finding of severe necrotic lesions that were observed in the basal ganglia (but not in the substantia nigra) of monkeys that received a single intracarotid injection of MPTP followed by gene therapy treatments. Although extensive unilateral dopaminergic nigrostriatal loss was found in all the animals, partial behavioral recovery was observed in the subjects that presented pallidal necrotic lesions. This report discusses possible causes and effects of the necrotic lesions and their locations and the value of the intracarotid MPTP model. Testing novel therapies in monkey models has become an essential step before clinical trials. These results indicate that evaluation of any treatment should consider possible confounding factors that may affect the results.