title: Developmental exposure to the organochlorine insecticide endosulfan alters expression of proteins associated with neurotransmission in the frontal cortex.
abstract: Exposure to environmental contaminants, such as organochlorine insecticides during critical periods of neurodevelopment has been shown to be a major contributor to several neuropsychological deficits seen in children, adolescence, and adults. Although the neurobehavioral outcomes resulting from exposure to these compounds are known the neurotransmitter circuitry and molecular targets that mediate these endpoints have not been identified. Given the importance of the frontal cortex in facilitating numerous neuropsychological processes, our current study sought to investigate the effects of developmental exposure to the organochlorine insecticide, endosulfan, on the expression of specific proteins associated with neurotransmission in the frontal cortex. Utilizing in vitro models we were able to show endosulfan reduces cell viability in IMR-32 neuroblastoma cells in addition to reducing synaptic puncta and neurite outgrowth in primary cultured neurons isolated from the frontal cortex of mice. Elaborating these findings to an in vivo model we found that developmental exposure of female mice to endosulfan during gestation and lactation elicited significant alterations to the GABAergic (GAT1, vGAT, GABAA receptor), glutamatergic (vGlut and GluN2B receptor), and dopaminergic (DAT, TH, VMAT2, and D2 receptor) neurotransmitter systems in the frontal cortex of male offspring. These findings identify damage to critical neurotransmitter circuits and proteins in the frontal cortex, which may underlie the neurobehavioral deficits observed following developmental exposure to endosulfan and other organochlorine insecticides.
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322-3090.
authors.forename: W Wyatt
authors.initials: WW
authors.lastname: Wilson
authors.forename: Wellington
authors.initials: W
authors.lastname: Onyenwe
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Bradner
authors.forename: Sadie E
authors.initials: SE
authors.lastname: Nennig
authors.forename: W Michael
authors.initials: WM
authors.lastname: Caudle
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004726:Endosulfan / Q000633:toxicity*; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D011963:Receptors, GABA-A; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D004726:Endosulfan
keywords: GABA; cognition; dopamine; glutamate; memory; schizophrenia