Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABA A antagonism

Neurotoxicology. 2016 Sep;56:86-93. doi: 10.1016/j.neuro.2016.07.006. Epub 2016 Jul 12.

Abstract

Developmental exposure of rats to polychlorinated biphenyls (PCBs) causes impairments in hearing and in the functioning of peripheral and central auditory structures. Additionally, recent work from our laboratory has demonstrated an increase in audiogenic seizures. The current study aimed to further characterize the effects of PCBs on auditory brain structures by investigating whether developmental exposure altered the magnitude of activation in the auditory cortex (AC) in response to electrical stimulation of thalamocortical afferents. Long-Evans female rats were fed cookies containing either 0 or 6mg/kg of an environmental PCB mixture daily from 4 weeks prior to breeding until postnatal day 21. Brain slices containing projections from the thalamus to the AC were collected from adult female offspring and were bathed in artificial cerebrospinal fluid (aCSF) alone, aCSF containing a gamma-aminobutyric acid (GABA) receptor antagonist (200nM SR95531), and aCSF containing an and N-methyl-d-aspartate (NMDA) receptor antagonist (50μM AP5). During each of these drug conditions, electrical stimulations ranging from 25 to 600μA were delivered to the thalamocortical afferents. Activation of the AC was measured using flavoprotein autofluorescence imaging. Although there were no differences seen between treatment groups in the aCSF condition, there were significant increases in the ratio of aCSF/SR95531 activation in slices from PCB-exposed animals compared to control animals. This effect was seen in both the upper and lower layers of the AC. No differences in activation were noted between treatment groups when slices were exposed to AP5. These data suggest that developmental PCB exposure leads to increased sensitivity to antagonism of GABAA receptors in the AC without a change in NMDA-mediated intrinsic excitability.

Keywords: Endocrine disruptor; GABA; Polychlorinated biphenyls.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology
  • Animals
  • Animals, Newborn
  • Auditory Cortex / drug effects*
  • Auditory Cortex / growth & development*
  • Electric Stimulation
  • Environmental Pollutants / toxicity*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • GABA-A Receptor Antagonists / pharmacology*
  • Male
  • Polychlorinated Biphenyls / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology
  • Pyridazines / pharmacology
  • Rats
  • Rats, Long-Evans
  • Valine / analogs & derivatives
  • Valine / pharmacology

Substances

  • Environmental Pollutants
  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Antagonists
  • Pyridazines
  • 2-amino-5-phosphopentanoic acid
  • gabazine
  • Polychlorinated Biphenyls
  • Valine