Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane

Neurotoxicology. 2007 Mar;28(2):415-20. doi: 10.1016/j.neuro.2006.03.006. Epub 2006 Mar 24.

Abstract

1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration-response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3 and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the delta subunit-containing GABAA receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Dose-Response Relationship, Drug
  • Excitatory Postsynaptic Potentials / drug effects
  • Gene Expression / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hydrocarbons, Brominated / chemistry
  • Hydrocarbons, Brominated / toxicity
  • Inhalation Exposure*
  • Male
  • Microinjections
  • Neocortex / drug effects
  • Neocortex / metabolism
  • Neural Inhibition / drug effects*
  • Neurotransmitter Agents / metabolism*
  • Neurotransmitter Agents / pharmacology
  • Oocytes
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Solvents / chemistry
  • Solvents / toxicity*
  • Volatilization
  • Xenopus laevis
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Gabrb3 protein, rat
  • Hydrocarbons, Brominated
  • Neurotransmitter Agents
  • RNA, Messenger
  • Receptors, GABA-A
  • Solvents
  • gamma-Aminobutyric Acid
  • 1-bromopropane