L-Deprenyl and MDL72974 do not improve the recovery of dopaminergic cells following systemic administration of MPTP in mouse.
L-Deprenyl, a monoamine oxidase B (MAO-B) inhibitor, administered prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) protects dopaminergic neurons against degeneration in several animal species including mice. L-Deprenyl inhibits MPP+ formation, the mediator of MPTP toxicity. In addition, L-deprenyl, administered 72 h following MPTP, improves the recovery of tyrosine hydroxylase (TH) immunopositive neurons in the substantia nigra (SN) of mice. This observation lead to the proposal that L-deprenyl exerts a 'neurorescue' effect. However, clinical trials failed to demonstrate that L-deprenyl can effectively 'rescues' degenerating dopaminergic neurons in early untreated Parkinson's disease (PD) patients. These observations prompted us to reevaluate the long-term impact of L-deprenyl on MPTP-induced dopaminergic cell loss in mice. In addition, we made use of another MAO-B inhibitor, MDL72974, to assess MAO-B participation in this paradigm. Our results suggest that L-deprenyl does not improve the recovery of TH immunopositive neurons in MPTP-treated mice. An apparent reduction in TH+ neurons is observed in the SN of MDL72974 and L-deprenyl/MPTP-treated mice at 30 days post-treatment. The possible implication of these findings in relation to the used of MAO-B inhibitors in PD is discussed.
Thiffault
C
C
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Lamarre-Théroux
L
L
Quirion
R
R
Poirier
J
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D002082:Butylamines / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents; D004353:Drug Evaluation, Preclinical; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*
D000498:Allyl Compounds; D002082:Butylamines; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; C058000:mofegiline; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine