title: Effects of environmentally relevant mixtures of persistent organic pollutants on the developmental neurobiology in rats.
abstract: We report the developmental neuropathology for rat pups at postnatal day (PND) 37 and PND 77 and the molecular biomarkers for PND 35, 75, and 350 after perinatal exposure to a reconstituted mixture of persistent organochlorine pollutants (POPs) based on the blood profiles of people living in the Great Lake Basin. The developmental neuropathology included routine histopathology evaluation, quantification of cell proliferation and death in the subventricular zone, linear morphometric measurements, and transcriptional analysis. No histopathological, structural, or stereological changes were observed in animals treated with the POPs or Aroclor 1254, on PND 37 or PND 77. While no transcriptional changes were found in Arcolor-treated animals, significant transcriptional changes were observed on PND 350 in female offspring perinatally exposed to 0.13 mg/kg of the POP mixture. Markers of the cholinergic system including acetylcholinesterase and the muscarinic receptors (subtypes M1-M5) were downregulated 2- to 6-fold. In addition, structural genes including neurofilaments (NFLs) and microtubule-associated protein (MAP-2) were downregulated at least 2-fold or greater. Our results support that in utero and lactational exposure to the chemical mixture of POPs lead to developmental changes in adult rat brains.
authors.affiliation: Toxicology Research Division, Health Products and Foods Branch, Health Canada, Ottawa, Ontario, Canada. santokh_gill@hc-sc.gc.ca
authors.forename: Santokh
authors.initials: S
authors.lastname: Gill
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Bowers
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Nakai
authors.forename: Al
authors.initials: A
authors.lastname: Yagminas
authors.forename: Rudi
authors.initials: R
authors.lastname: Mueller
authors.forename: Olga
authors.initials: O
authors.lastname: Pulido
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D045424:Complex Mixtures / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D045424:Complex Mixtures; D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger