title: A single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice.
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.
authors.affiliation: a Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University Greenville , NC , USA.
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Meadows
authors.affiliation: a Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University Greenville , NC , USA.
authors.forename: Chevonne
authors.initials: C
authors.lastname: Parker
authors.affiliation: b Department of Microbiology and Immunology , UAMS College of Medicine, Arkansas Children's Research Institute , Little Rock , AR , USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gilbert
authors.affiliation: c Department of Pediatrics , UAMS College of Medicine, Arkansas Children's Research Institute , Little Rock , AR , USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Blossom
authors.affiliation: a Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University Greenville , NC , USA.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: DeWitt
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004787:Environmental Pollution / Q000009:adverse effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D020078:Neurogenic Inflammation / Q000276:immunology*; D018384:Oxidative Stress; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D014241:Trichloroethylene / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; D016753:Interleukin-10; D014241:Trichloroethylene
keywords: Trichloroethylene; brain; developmental; early-life; microglia; neuroinflammation