Rescue of dying neurons by (R)-deprenyl in the MPTP-mouse model of Parkinson's disease does not include restoration of neostriatal dopamine.
Chronic (8- to 10-week) administration of the selective, potent, and irreversible monoamine oxidase B inhibitor (R)-deprenyl has been shown to increase the tyrosine hydroxylase immunoreactivity in the substantia nigra of mice that had been treated three days earlier with a neurotoxic dose of the parkinsonian-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This reported rescuing of lesioned nigrostriatal cell bodies by (R)-deprenyl prompted us to investigate if this (R)-deprenyl treatment also could restore neostriatal dopamine levels that are depleted by MPTP. The results of these experiments show that long term (8 or 10 weeks) treatment with (R)-deprenyl beginning three days post MPTP administration did not result in restoration of depleted neostriatal dopamine levels in C57BL/6 mice. We conclude that, although (R)-deprenyl may rescue MPTP-injured nigrostriatal neurons, it does not lead to functional recovery of these neurons as measured by the restoration of neostriatal dopamine levels.
Steyn
S J
SJ
Harvey W. Peters Center for the Study of Parkinson's Disease, Department of Chemistry, Virginia Tech., Blacksburg, VA 24061-0212, USA.
Castagnoli
K
K
Castagnoli
N
N
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism*; D012642:Selegiline / Q000494:pharmacology* / Q000627:therapeutic use
D000978:Antiparkinson Agents; D012642:Selegiline; D004298:Dopamine