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Title: Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation

Abstract

Exposure to polychlorinated biphenyls impairs cognition and behavior in children. Two environmental PCBs 2,2',3,3',4,4',5-heptachlorobiphenyl (PCB170) and 2,2',3,5',6-pentachlorobiphenyl (PCB95) were examined in vitro for influences on synaptic transmission in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region using a multi-electrode array. Perfusion with PCB170 (10 nM) had no effect on fEPSP slope relative to baseline period, whereas (100 nM) initially enhanced then depressed fEPSP slope. Perfusion of PCB95 (10 or 100 nM) persistently enhanced fEPSP slope > 200%, an effect that could be inhibited by dantrolene, a drug that attenuates ryanodine receptor signaling. Perfusion with picrotoxin (PTX) to block GABA neurotransmission resulted in a modest increase in fEPSP slope, whereas PTX + PCB170 (1-100 nM) persistently enhanced fEPSP slope in a dose dependent manner. fEPSP slope reached > 250% of baseline period in the presence of PTX + 100 nM PCB170, conditions that evoked marked epileptiform after-potential discharges. PCB95 and PCB170 were found to differentially influence the Ca{sup 2+}-dependence of [{sup 3}H]ryanodine-binding to hippocampal ryanodine receptors. Non-coplanar PCB congeners can differentially alter neurotransmission in a manner suggesting they can elicit imbalances between inhibitory and excitatory circuits within the hippocampus. Differential sensitization of ryanodine receptors bymore » Ca{sup 2+} appears to mediate, at least in part, hippocampal excitotoxicity by non-coplanar PCBs.« less

Authors:
 [1]; ;  [2]
  1. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, 95616 (United States)
  2. Department of Neurological Surgery, School of Medicine, University of California, Davis, California (United States)
Publication Date:
OSTI Identifier:
21272566
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 237; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2009.03.002; PII: S0041-008X(09)00105-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; HIPPOCAMPUS; HYDROXYLASES; IN VITRO; LABELLED COMPOUNDS; POLYCHLORINATED BIPHENYLS; RECEPTORS; TRITIUM COMPOUNDS

Citation Formats

Kim, Kyung Ho, Inan, Salim Yalcin, Berman, Robert F, and Pessah, Isaac N. Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation. United States: N. p., 2009. Web. doi:10.1016/j.taap.2009.03.002.
Kim, Kyung Ho, Inan, Salim Yalcin, Berman, Robert F, & Pessah, Isaac N. Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation. United States. https://doi.org/10.1016/j.taap.2009.03.002
Kim, Kyung Ho, Inan, Salim Yalcin, Berman, Robert F, and Pessah, Isaac N. Mon . "Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation". United States. https://doi.org/10.1016/j.taap.2009.03.002.
@article{osti_21272566,
title = {Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation},
author = {Kim, Kyung Ho and Inan, Salim Yalcin and Berman, Robert F and Pessah, Isaac N.},
abstractNote = {Exposure to polychlorinated biphenyls impairs cognition and behavior in children. Two environmental PCBs 2,2',3,3',4,4',5-heptachlorobiphenyl (PCB170) and 2,2',3,5',6-pentachlorobiphenyl (PCB95) were examined in vitro for influences on synaptic transmission in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region using a multi-electrode array. Perfusion with PCB170 (10 nM) had no effect on fEPSP slope relative to baseline period, whereas (100 nM) initially enhanced then depressed fEPSP slope. Perfusion of PCB95 (10 or 100 nM) persistently enhanced fEPSP slope > 200%, an effect that could be inhibited by dantrolene, a drug that attenuates ryanodine receptor signaling. Perfusion with picrotoxin (PTX) to block GABA neurotransmission resulted in a modest increase in fEPSP slope, whereas PTX + PCB170 (1-100 nM) persistently enhanced fEPSP slope in a dose dependent manner. fEPSP slope reached > 250% of baseline period in the presence of PTX + 100 nM PCB170, conditions that evoked marked epileptiform after-potential discharges. PCB95 and PCB170 were found to differentially influence the Ca{sup 2+}-dependence of [{sup 3}H]ryanodine-binding to hippocampal ryanodine receptors. Non-coplanar PCB congeners can differentially alter neurotransmission in a manner suggesting they can elicit imbalances between inhibitory and excitatory circuits within the hippocampus. Differential sensitization of ryanodine receptors by Ca{sup 2+} appears to mediate, at least in part, hippocampal excitotoxicity by non-coplanar PCBs.},
doi = {10.1016/j.taap.2009.03.002},
url = {https://www.osti.gov/biblio/21272566}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 237,
place = {United States},
year = {2009},
month = {6}
}