Advanced

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

Côté, M; Drouin-Ouellet, J LU ; Cicchetti, F and Soulet, D LU (2011) In Brain Behavior and Immunity 25(6). p.52-1143
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
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
in
Brain Behavior and Immunity
volume
25
issue
6
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:79960282591
ISSN
1090-2139
DOI
10.1016/j.bbi.2011.02.017
language
English
LU publication?
no
id
bb7bdca1-7e90-4f74-8774-fb99d8034701
date added to LUP
2016-11-22 09:05:34
date last changed
2017-11-17 09:24:57
@article{bb7bdca1-7e90-4f74-8774-fb99d8034701,
  abstract     = {<p>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.</p>},
  author       = {Côté, M and Drouin-Ouellet, J and Cicchetti, F and Soulet, D},
  issn         = {1090-2139},
  keyword      = {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},
  language     = {eng},
  number       = {6},
  pages        = {52--1143},
  publisher    = {Elsevier},
  series       = {Brain Behavior and Immunity},
  title        = {The critical role of the MyD88-dependent pathway in non-CNS MPTP-mediated toxicity},
  url          = {http://dx.doi.org/10.1016/j.bbi.2011.02.017},
  volume       = {25},
  year         = {2011},
}