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Prenatal Exposure to Neurotoxicants Dieldrin or Lindane Alters tert-ButylbicyclophosphorothionateBinding to GABA A Receptors in Fetal Rat Brainstem

Authors
  • Brannen, Kimberly C.
  • Devaud, Leslie L.
  • Liu, Jiangping
  • Lauder, Jean M.
Type
Published Article
Journal
Developmental Neuroscience
Publisher
S. Karger AG
Publication Date
Feb 01, 1998
Volume
20
Issue
1
Pages
34–41
Identifiers
DOI: 10.1159/000017296
Source
Karger
Keywords
License
Green
External links

Abstract

GABA acts as a trophic signal for cultured embryonic rat monoamine neurons by activating GABAA receptors. These effects are blocked by the organochlorine insecticide dieldrin and the classic GABAA antagonist bicuculline. Both dieldrin and another organochlorine insecticide, lindane, block the effects of GABA on the GABAA receptor by binding directly to the Cl– channel. Therefore, prenatal exposure to these chemicals could lead to disturbances in the trophic actions of GABA on monoamine neurotransmitter systems in the embryonic brain and produce alterations in GABAA receptor expression and function. Effects of daily prenatal exposure to organochlorine insecticide (dieldrin or lindane) or bicuculline from embryonic day (E)12–17 were determined in brains of E17 fetal rats using t-[35S]butyl-bicyclophosphorothionate ([35S]TBPS) binding. This radioligand was chosen because, like organochlorine insecticides, it binds directly to GABAA receptor/Cl– channels. [35S]TBPS binding was analyzed in extensively washed membranes from E17 brainstem and whole brain with the brainstem removed (‘rest of brain’) at a TBPS concentration that approximated the KD determined in [35S]TBPS saturation binding experiments performed on normal E17 rat brainstem. In utero exposure to dieldrin, lindane, or bicuculline from E12-E17 caused a significant reduction in the amount of [35S]TBPS binding in E17 brainstem compared to vehicle-injected controls, but had no significant effect on ‘rest of brain’. These data suggest that in utero exposure to organochlorine insecticides that act as GABAA antagonists negatively regulate expression of GABAA receptors in fetal brainstem. If these effects persist, they could lead to disturbances in postnatal functions of the ascending GABAergic system, possibly with behavioral consequences.

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