The critical role of the MyD88-dependent pathway in non-CNS MPTP-mediated toxicity

Research output: Contribution to journalArticle

Abstract

A growing body of evidence supports a role of inflammation in the loss of central nervous system neurons both to acute and chronic insults, while its contribution to the loss of neurons in the enteric nervous system remains largely uninvestigated. We have addressed this issue by exploring the role of inflammation in dopaminergic (DAergic) myenteric neuronal degeneration secondary to MPTP lesioning in mice deficient in MyD88, a protein implicated in the cascade of events leading to the innate immune response. Our results show that MPTP-treated MyD88 knock out (MyD88(-/-)) mice were protected against the toxin-induced TH-immunoreactive neuronal degeneration at the level of the myenteric plexus of the distal ileum, which causes a 50% loss of such neurons in MPTP-treated WT mice. Interestingly, the density of macrophages was the same in the MyD88(-/-) mice subjected to MPTP, as opposed to the increase in density observed in wild-type (WT) mice treated with the toxin, which was due to an infiltration of monocyte from the blood to the myenteric tissue. Furthermore, in MPTP-treated MyD88(-/-) mice, resident macrophages exhibited a predominant pro-repair phenotype, which could have contributed to the protection of DAergic neurons in the myenteric plexus. Taken together, our results suggest a critical role for the MyD88-dependent pathway in the gastrointestinal DAergic degeneration induced by MPTP.

Details

Authors
  • M Côté
  • J Drouin-Ouellet
  • F Cicchetti
  • D Soulet
External organisations
  • Centre Hospitalier de l'Universite Laval (CHUL)
  • Laval University
Research areas and keywords

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Dopamine, Ileitis, Ileum, Immunity, Innate, Immunity, Mucosal, Intestinal Mucosa, MPTP Poisoning, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88, Myenteric Plexus, Nerve Degeneration, Neuroimmunomodulation, Neurons, Neurotoxins, Neutrophils, Tyrosine 3-Monooxygenase, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)1143-52
Number of pages10
JournalBrain Behavior and Immunity
Volume25
Issue number6
Publication statusPublished - 2011 Aug
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes