Neuroinflammation in organophosphate-induced neurotoxicity

Michelle Guignet, Pamela J. Lein

Research output: Chapter in Book/Report/Conference proceedingChapter

15 Scopus citations

Abstract

Organophosphates (OPs) are a group of synthetic compounds that are neurotoxic in humans and preclinical models. The canonical mechanism of OP neurotoxicity is inhibition of acetylcholinesterase (AChE). However, multiple lines of evidence suggest that mechanisms in addition to or other than AChE inhibition contribute to the long-term effects associated with acute OP intoxication and to neurobehavioral deficits linked to repeated, subclinical OP exposures. It is widely posited that neuroinflammation contributes, at least in part, to the neurotoxic effects of OPs. This hypothesis is largely derived from preclinical studies demonstrating that OPs trigger neuroinflammatory responses, and from clinical and preclinical data implicating neuroinflammation in the pathogenesis of neurological diseases with phenotypic outcomes similar to those associated with neurotoxic OP exposures. However, the mechanism(s) by which OPs cause neuroinflammation and the pathophysiologic relevance of neuroinflammation in OP neurotoxicity remain pressing questions for which there are currently limited data. The goals of this chapter are to: (i) summarize the evidence documenting that not only acute OP intoxication but also repeated subclinical OP exposures elicit neuroinflammatory responses; (ii) discuss mechanisms hypothesized to mediate OP-induced neuroinflammation; (iii) review the available evidence suggesting that neuroinflammation may contribute to the pathogenesis of OP neurotoxicity and/or neuroprotective mechanisms triggered in response to OP-induced injury; and (iv) identify critical data gaps that need to be addressed to better understand the diagnostic and therapeutic implications of OP-induced neuroinflammation.

Original languageEnglish (US)
Title of host publicationRole of Inflammation in Environmental Neurotoxicity
EditorsMichael Aschner, Lucio G. Costa, Lucio G. Costa
PublisherElsevier Inc.
Pages35-79
Number of pages45
ISBN (Print)9780128157176
DOIs
StatePublished - Jan 2019

Publication series

NameAdvances in Neurotoxicology
Volume3
ISSN (Electronic)2468-7480

Keywords

  • Chlorpyrifos
  • Diisopropylfluorophosphate
  • Microglial activation
  • OP nerve agents
  • OP neurotoxicity
  • OP pesticides
  • Proinflammatory cytokines
  • Reactive astrogliosis
  • Status epilepticus

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Health, Toxicology and Mutagenesis

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