Astrocytes as a primary locus for the conversion MPTP into MPP+

W. J. Brooks, M. F. Jarvis, G. C. Wagner

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The enzymatic conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenylpyridinium ion by monoamine oxidase-B is an essential step mediating the dopaminergic neurotoxicity. Since monoamine oxidase-B is located primarily in serotonergic neurons and astrocytes, the production of 1-methyl-4-phenylpyridinium ion is thought to be extra-dopaminergic. This study provides evidence in support of this conclusion. Pretreating mice with fluoxetine (a serotonergic uptake inhibitor) before the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine attenuated the dopaminergic neurotoxicity. This was not the result of a nonspecific inhibition of dopaminergic uptake, as fluoxetine pretreatment did not attenuate the dopaminergic neurotoxicity resulting from the intrastriatal administration of the 1-methyl-4-phenylpyridinium ion. Further localization of the primary site of 1-methyl-4-phenylpyridinium ion production as being astrocytes was provided by the failure of 5,7-dihydroxytryptamine-induced serotonergic lesions to attenuate the neurotoxicity produced by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, whereas, fluoxetine pretreatment in similarly lesioned subjects, continued to attenuate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity. These results are consistent with the hypothesis that astrocytes are a principle site of 1-methyl-4-phenylpyridinium ion production.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of Neural Transmission
Volume76
Issue number1
DOIs
StatePublished - Feb 1 1989

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Keywords

  • Dopamine
  • MPTP
  • astrocyte
  • fluoxetine
  • serotonin

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