Neural progenitor cells are protected against MPTP by MAO-B inhibitors.
Neurotoxic effects of MPTP on the nigrostriatal dopaminergic system are thought to be initiated by 1-methyl-4-phenylpyridinium (MPP+), a metabolite formed by the monoamine oxidase (MAO)-B-mediated oxidation of MPTP. We previously reported that the administration of MPTP induced apoptosis in migrating neuroblasts (neural progenitor cells, NPCs) in adult mice. To determine whether MAO-B is also involved in the neurotoxicity of MPTP to NPCs, this study looked at the effects of MAO B inhibitors, R(-)-deprenyl (deprenyl) and N-(2-aminoethyl)-4-chlorobenzamide (Ro 16-6491), both of which protect the dopaminergic system against MPTP. Few apoptotic cells were found in saline- or MAO-B inhibitor-treated animals but MPTP markedly induced apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) after 1 day. When mice were pretreated with deprenyl or Ro 16-6491, not only nigrostriatal dopamine levels but also NPCs were significantly protected against MPTP. In addition, MPTP-induced apoptosis was found in both juvenile (postnatal 21 days) and older (12 months old) mice, suggesting NPCs to be different from the dopamine system, which has been thought to exhibit age-dependent susceptibility to MPTP.
He
Xi Jun
XJ
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan. aaa37172@mail.goo.ne.jp
Uetsuka
Koji
K
Nakayama
Hiroyuki
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D053687:Adult Stem Cells / Q000187:drug effects*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D012642:Selegiline; C051040:Ro 16-6491; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase