title: Perinatal exposure to environmental polychlorinated biphenyls sensitizes hippocampus to excitotoxicity ex vivo.
abstract: Ortho-substituted polychlorinated biphenyls (PCBs) are a concern to human developmental health. Rat dams were exposed to an environmentally relevant mixture of PCBs, Aroclor 1254, or pure congener PCB 95 (6 mg/kg/day) during the perinatal period (GD 5 through PD 21). Hippocampal slices prepared from offspring 1-3 weeks post-weaning were tested for persisting changes in sensitivity to the excitotoxicant picrotoxin. Hippocampal slices were placed on multielectrode arrays. Field excitatory postsynaptic potentials (fEPSPs) were recorded from Schaffer Collateral/Commissural fibers in striatum radiatum of the CA1 region in response to single pulse stimuli. After recording baseline excitability, GABA(A) receptors were blocked by inclusion of picrotoxin (100 μM) in the aCSF perfusate. Picrotoxin produced negligible changes in fEPSP slope in slices isolated from offspring exposed to vehicle, whereas slices from either PCB test group invariably showed >200% (p<0.01) synaptic facilitation. Picrotoxin produced prominent after-discharges (epileptic wave forms) in the evoked potentials measured from PCB exposed, but not control, hippocampal slices. These results show that developmental exposure to non-coplanar PCBs is sufficient to produce changes in synaptic plasticity that can be unmasked in the presence of GABA(A) receptor deficits that persist 1-3 weeks after exposure ceased. Developmental exposure to PCBs may sensitize seizure susceptibility postnatally, especially in susceptible populations with GABA(A) receptor signaling deficits.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
mesh_terms: D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D004558:Electric Stimulation; D004785:Environmental Pollutants / Q000633:toxicity*; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D018811:Maternal Exposure; D009473:Neuronal Plasticity / Q000187:drug effects; D010852:Picrotoxin / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D020111:Chlorodiphenyl (54% Chlorine); D004785:Environmental Pollutants; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D011078:Polychlorinated Biphenyls; C032904:2,2',3,5',6-pentachlorobiphenyl