PMID- 19616025 OWN - NLM STAT- MEDLINE DCOM- 20100309 LR - 20221207 IS - 1872-9711 (Electronic) IS - 0161-813X (Linking) VI - 30 IP - 6 DP - 2009 Nov TI - MPTP-induced neuroblast apoptosis in the subventricular zone is not regulated by dopamine or other monoamine transporters. PG - 1036-44 LID - 10.1016/j.neuro.2009.07.003 [doi] AB - 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. FAU - Shibui, Yusuke AU - Shibui Y AD - 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 FAU - He, Xi Jun AU - He XJ FAU - Uchida, Kazuyuki AU - Uchida K FAU - Nakayama, Hiroyuki AU - Nakayama H LA - eng PT - Journal Article DEP - 20090716 PL - Netherlands TA - Neurotoxicology JT - Neurotoxicology JID - 7905589 RN - 0 (Adrenergic Uptake Inhibitors) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotoxins) RN - 0 (Neurotransmitter Transport Proteins) RN - 0 (Piperazines) RN - 0 (Serotonin Uptake Inhibitors) RN - 01K63SUP8D (Fluoxetine) RN - 90X28IKH43 (vanoxerine) RN - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) RN - TG537D343B (Desipramine) RN - Z9O08YRN8O (Tetrabenazine) SB - IM MH - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*pharmacology MH - Adrenergic Uptake Inhibitors/pharmacology MH - Adult Stem Cells/*drug effects MH - Animals MH - Apoptosis/*drug effects MH - Cerebral Ventricles/*cytology/drug effects MH - Desipramine/pharmacology MH - Dopamine Uptake Inhibitors/pharmacology MH - Drug Interactions MH - Fluoxetine/pharmacology MH - Gene Expression Regulation/drug effects MH - In Situ Nick-End Labeling MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/metabolism MH - Neurotoxins/*pharmacology MH - Neurotransmitter Transport Proteins/genetics/*metabolism MH - Piperazines/pharmacology MH - Selective Serotonin Reuptake Inhibitors/pharmacology MH - Tetrabenazine/pharmacology EDAT- 2009/07/21 09:00 MHDA- 2010/03/10 06:00 CRDT- 2009/07/21 09:00 PHST- 2009/01/13 00:00 [received] PHST- 2009/07/05 00:00 [revised] PHST- 2009/07/07 00:00 [accepted] PHST- 2009/07/21 09:00 [entrez] PHST- 2009/07/21 09:00 [pubmed] PHST- 2010/03/10 06:00 [medline] AID - S0161-813X(09)00157-0 [pii] AID - 10.1016/j.neuro.2009.07.003 [doi] PST - ppublish SO - Neurotoxicology. 2009 Nov;30(6):1036-44. doi: 10.1016/j.neuro.2009.07.003. Epub 2009 Jul 16.