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Related Experiment Videos

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

W J Brooks1, M F Jarvis, G C Wagner

  • 1Department of Psychology, Rutgers, State University, New Brunswick, New Jersey.

Journal of Neural Transmission
|January 1, 1989
PubMed
Summary

Monoamine oxidase-B converts MPTP to MPP+, causing neurotoxicity. This study shows astrocytes, not dopamine neurons, are the primary site of this conversion, evidenced by fluoxetine

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Area of Science:

  • Neuroscience
  • Toxicology
  • Biochemistry

Background:

  • Monoamine oxidase-B (MAO-B) mediates dopaminergic neurotoxicity via MPTP conversion.
  • MAO-B's presence in serotonergic neurons and astrocytes suggests extra-dopaminergic MPP+ production.

Purpose of the Study:

  • To investigate the primary site of MPP+ production and its role in neurotoxicity.
  • To determine if astrocytes are the main site for MPP+ synthesis.

Main Methods:

  • Mice were pretreated with fluoxetine (serotonin uptake inhibitor) before MPTP administration.
  • Neurotoxicity was assessed after intrastriatal MPP+ administration.
  • Serotonergic neurons were lesioned using 5,7-dihydroxytryptamine.

Main Results:

Related Experiment Videos

  • Fluoxetine pretreatment attenuated MPTP-induced neurotoxicity.
  • Fluoxetine did not affect neurotoxicity from direct MPP+ administration.
  • Serotonergic lesions did not prevent MPTP neurotoxicity, but fluoxetine still provided protection.

Conclusions:

  • Astrocytes are a principal site for MPP+ production.
  • MPP+ neurotoxicity is primarily mediated by extra-dopaminergic pathways involving astrocytes.