title: An in vivo animal study assessing long-term changes in hypothalamic cytokines following perinatal exposure to a chemical mixture based on Arctic maternal body burden.
abstract: BACKGROUND
  The geographic distribution of environmental toxins is generally not uniform, with certain northern regions showing a particularly high concentration of pesticides, heavy metals and persistent organic pollutants. For instance, Northern Canadians are exposed to high levels of persistent organic pollutants like polychlorinated biphenyls (PCB), organochlorine pesticides (OCs) and methylmercury (MeHg), primarily through country foods. Previous studies have reported associations between neuronal pathology and exposure to such toxins. The present investigation assessed whether perinatal exposure (gestation and lactation) of rats to a chemical mixture (27 constituents comprised of PCBs, OCs and MeHg) based on Arctic maternal exposure profiles at concentrations near human exposure levels, would affect brain levels of several inflammatory cytokines
  
  
  METHODS
  Rats were dosed during gestation and lactation and cytokine levels were measured in the brains of offspring at five months of age. Hypothalamic cytokine protein levels were measured with a suspension-based array system and differences were determined using ANOVA and post hoc statistical tests.
  
  
  RESULTS
  The early life PCB treatment alone significantly elevated hypothalamic interleukin-6 (IL-6) levels in rats at five months of age to a degree comparable to that of the entire chemical mixture. Similarly, the full mixture (and to a lesser degree PCBs alone) elevated levels of the pro-inflammatory cytokine, IL-1b, as well as the anti-inflammatory cytokine, IL-10. The full mixture of chemicals also moderately increased (in an additive fashion) hypothalamic levels of the pro-inflammatory cytokines, IL-12 and tumor necrosis factor (TNF-α). Challenge with bacterial endotoxin at adulthood generally increased hypothalamic levels to such a degree that differences between the perinatally treated chemical groups were no longer detectable.
  
  
  CONCLUSIONS
  These data suggest that exposure at critical neurodevelopmental times to environmental chemicals at concentrations and combinations reflective of those observed in vulnerable population can have enduring consequences upon cytokines that are thought to contribute to a range of pathological states. In particular, such protracted alterations in the cytokine balance within the hypothalamus would be expected to favor marked changes in neuro-immune and hormonal communication that could have profound behavioral consequences.
authors: Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, K1S 5B6, Canada. shawn_hayley@carleton.ca
authors: Shawn
authors: S
authors: Hayley
authors: Emily
authors: E
authors: Mangano
authors: Geoffrey
authors: G
authors: Crowe
authors: Nanqin
authors: N
authors: Li
authors: Wayne J
authors: WJ
authors: Bowers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001110:Arctic Regions; D001822:Body Burden; D002170:Canada; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007031:Hypothalamus / Q000187:drug effects* / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000032:analysis / Q000276:immunology; D007774:Lactation; D008070:Lipopolysaccharides / Q000276:immunology; D018811:Maternal Exposure; D008767:Methylmercury Compounds / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D051381:Rats; D013995:Time; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D007378:Interleukins; D008070:Lipopolysaccharides; D008767:Methylmercury Compounds; D014409:Tumor Necrosis Factor-alpha; D011078:Polychlorinated Biphenyls