A single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice

Jacqueline R Meadows,Chevonne Parker,Kathleen M Gilbert,Sarah J Blossom,Jamie C Dewitt

doi:10.1080/1547691x.2017.1305021

Jacqueline R Meadows, Chevonne Parker + Show 3 more

Open Access

https://doi.org/10.1080/1547691x.2017.1305021

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Abstract

Trichloroethylene (TCE) is a widespread environmental contaminant associated with developmental immunotoxicity and neurotoxicity. Previous studies have shown that MRL+/+ mice exposed to TCE from gestation through early-life demonstrate robust increases in inflammatory markers in peripheral CD4+ T-cells, as well as glutathione depletion and increased oxidative stress in cerebellum-associated with alterations in behavior. Since increased oxidative stress is associated with neuroinflammation, we hypothesized that neuroinflammatory markers could be altered relative to unexposed mice. MRL+/+ mice were given 0.5 mg/ml of TCE in vehicle or vehicle (water with 1% Alkamuls EL-620) from conception through early adulthood via drinking water to dams and then directly to post-weaning offspring. Animals were euthanized at 49 days of age and levels of pro- and anti-inflammatory cytokines, density of T-cell staining, and micro-glial morphology were evaluated in brains to begin to ascertain a neuroinflammatory profile. Levels of IL-6 were decreased in female animals and while not statistically significant, and levels of IL-10 were higher in brains of exposed male and female animals. Supportive of this observation, although not statistically significant, the number of ameboid microglia was higher in exposed relative to unexposed animals. This overall profile suggests the emergence of an anti-inflammatory/neuroprotective phenotype in exposed animals, possibly as a compensatory response to neuroinflammation that is known to be induced by developmental exposure to TCE.

Highlights

Trichloroethylene (TCE) is an organic solvent most commonly used as a degreasing agent in myriad industrial settings
The exposure levels of TCE resulting from maternal exposure were not determined, the dose of TCE from direct exposure (PND21-PND49) were lower than the current 8-h Permissible Exposure Limit (PEL) established by the Occupational Safety and Health Administration (OSHA) for TCE of 100 ppm [or ≈76 mg/kg/day]
Developmental exposure to TCE has been associated with both immunotoxicity and neurotoxicity in an MRL+/+ mouse model as well as in humans occupationally exposed to relatively high levels of TCE

Summary

Introduction

Trichloroethylene (TCE) is an organic solvent most commonly used as a degreasing agent in myriad industrial settings. Systemic effects may be contributing to TCE-induced developmental neurotoxicity via crosstalk between immune cells in the periphery and in the central nervous system (CNS) This crosstalk may occur indirectly via the production of inflammatory mediators in the periphery or directly through interaction of brain-infiltrating CD4+ T-cells with microglia, the resident macrophages of the CNS, and other cell types in the CNS. While both scenarios are plausible, studies to determine a causative role for CD4+ T-cells in mediating this neurotoxicity, either by using knockout mice or adoptive transfer experiments, have not been conducted

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