title: MPTP-induced neuroblast apoptosis in the subventricular zone is not regulated by dopamine or other monoamine transporters.
abstract: For 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to exert neurotoxicity on dopaminergic neurons, 1-methyl-4-phenylpyridinium (MPP+), a metabolite of MPTP, must be taken up into the dopaminergic neuron via the dopamine transporter (DAT). Previous reports have shown that MPTP also causes neuroblast apoptosis in the subventricular zone (SVZ) of adult mice. The aim of this study is to elucidate the role of DAT and other monoamine transporters including vesicular monoamine transporter 2 (VMAT2), the serotonin transporter (SERT), and the norepinephrine transporter (NET) on the neuroblast apoptosis induced by MPTP administration. There were no DAT-positive neuroblasts in the SVZ, whereas some neuroblasts were immunopositive for VMAT2 and SERT. To examine whether these transporters are involved in MPTP-induced neuroblast apoptosis in the SVZ, terminal deoxynucleotidyl transferase-mediated dUTP endlabeling (TUNEL)-positive cells were semiquantitatively analyzed after the injection of GBR12909 (GBR), a DAT inhibitor; tetrabenazine (TBZ), a VMAT2 inhibitor; fluoxetine (FLU), a SERT inhibitor, or desipramine (DES), a NET inhibitor, prior to MPTP injection. However, the injection of these transporter inhibitors had no influence on the MPTP-induced neuroblast apoptosis in the SVZ. It is likely that neither DAT nor other monoamine transporters are involved in MPTP-induced neuroblast apoptosis. The present findings suggest that the neurotoxicity of MPTP to neuroblasts in the SVZ does not require DAT or other monoamine transporters, and the apoptosis it induces may be executed through other unknown pathways.
authors.affiliation: 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. maron2005@live.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shibui
authors.forename: Xi Jun
authors.initials: XJ
authors.lastname: He
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D053687:Adult Stem Cells / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000166:cytology* / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D050479:Neurotransmitter Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013747:Tetrabenazine / Q000494:pharmacology
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D018759:Adrenergic Uptake Inhibitors; D003891:Desipramine; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D050479:Neurotransmitter Transport Proteins; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013747:Tetrabenazine; C043425:vanoxerine