title: Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus.
abstract: Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC.
authors.affiliation: *Neuroscience Program and sbandara@ucdavis.edu.
authors.forename: Suren B
authors.initials: SB
authors.lastname: Bandara
authors.affiliation: *Neuroscience Program and Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, Urbana, Illinois 61802; and.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Eubig
authors.affiliation: *Neuroscience Program and Beckman Institute, University of Illinois, Urbana-Champaign, Urbana, Illinois 60801.
authors.forename: Renee N
authors.initials: RN
authors.lastname: Sadowski
authors.affiliation: *Neuroscience Program and Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, Urbana, Illinois 61802; and Beckman Institute, University of Illinois, Urbana-Champaign, Urbana, Illinois 60801.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schantz
mesh_terms: D000818:Animals; D020195:Epilepsy, Reflex / Q000139:chemically induced*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D007245:Inferior Colliculi / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D011078:Polychlorinated Biphenyls; D005968:Glutamate Decarboxylase
keywords: GAD; IC; PCBs; audiogenic seizures