Low nigrostriatal reserve for motor parkinsonism in nonhuman primates

• Published in: Experimental neurology 2012-10, Vol.237 (2), p.355-362
• Main Authors: Tabbal, Samer D., Tian, LinLin, Karimi, Morvarid, Brown, Christopher A., Loftin, Susan K., Perlmutter, Joel S.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chromatography, High Pressure Liquid; Corpus Striatum - chemistry; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine; Dopamine - analysis; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Immunohistochemistry; Indexing in process; Macaca; Male; Medical sciences; MPTP; Neurology; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - pathology; Parkinsonism; Substantia nigra; Substantia Nigra - pathology
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2012.07.008

Nigrostriatal reserve refers to the threshold of neuronal injury to dopaminergic cell bodies and their terminal fields required to produce parkinsonian motor deficits. Inferential studies have estimated striatal dopamine reserve to be at least 70%. Knowledge of this threshold is critical for planning interventions to prevent symptom onset or reverse nigrostriatal injury sufficient to restore function in people with Parkinson disease. In this study, we determine the nigrostriatal reserve in a non-human primate model that mimics the motor manifestations of Parkinson disease. Fifteen macaque monkeys received unilateral randomized doses of the selective dopaminergic neuronal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We compared blinded validated ratings of parkinsonism to in vitro measures of striatal dopamine and unbiased stereologic counts of nigral neurons after tyrosine hydroxylase immunostaining. The percent of residual cell counts in lesioned nigra correlated linearly with the parkinsonism score at 2months (r=−0.87, p