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Interleukin-18 null mice show diminished microglial activation and reduced dopaminergic neuron loss following acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment

Academic Article
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Overview

authors

  • Sugama, S.
  • Wirz, S. A.
  • Barr, A. M.
  • Conti, Bruno
  • Bartfai, Tamas
  • Shibasaki, T.

publication date

  • 2004

journal

  • Neuroscience  Journal

abstract

  • Recent reports have revealed an involvement of microglial cells in dopaminergic neurodegeneration. In the present study, we tested the hypothesis that interleukin-18 (IL-18) plays a role in the microglial activation. The present study investigated microglial activation and dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in wild type (WT) and IL-18 knockout (KO) mice. The number of dopaminergic neuron loss in WT mice was significantly decreased 7 days after MPTP treatment compared with IL-18 KO mice. In WT mice microglial activation occurred in the SN at 1 day after MPTP treatment, progressively increased within the SNpc until 7 days post MPTP, and subsided by 14 days. In contrast, in IL-18 KO mice microglial activation occurred in the SN at 1 day post-MPTP, and decreased by 7 days, earlier than in WT mice. The lesser microglial activation and dopaminergic neurodegeneration in the SNpc following MPTP treatment in WT indicates the possibility that IL-18 may participate in microglial activation and dopaminergic neurodegeneration.

subject areas

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Cell Count
  • Corpus Striatum
  • Dopamine
  • Dopamine Agents
  • Immunohistochemistry
  • Interleukin-18
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia
  • Nerve Degeneration
  • Neurons
  • Staining and Labeling
  • Substantia Nigra
  • Tyrosine 3-Monooxygenase
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Research

keywords

  • MPTP
  • dopaminergic neurons
  • interleukin-18
  • microglia
  • substantia nigra
  • tyrosine hydroxylase
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Identity

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/j.neuroscience.2004.07.020

PubMed ID

  • 15350655
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Additional Document Info

start page

  • 451

end page

  • 458

volume

  • 128

issue

  • 2

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