Effect of gamma-hexachlorocyclohexane and its isomers on proto-oncogene c-fos expression in brain

M Vendrell1, J M Tusell, J Serratosa

  • 1Dept. de Farmacologia i Toxicologia, CID-CSIC, Barcelona, Spain.

Neurotoxicology
|January 1, 1992
PubMed

Insights

This study shows that the insecticide lindane and convulsants like PTZ and PTX can increase c-fos gene expression in rat brains. This c-fos mRNA distribution may serve as a marker for neurotoxic effects.

Area of Science:

  • Neuroscience
  • Toxicology
  • Molecular Biology

Background:

  • Proto-oncogene c-fos expression is a marker for neuronal activity.
  • Organochlorine insecticides and convulsants can affect brain function.
  • Understanding neurotoxic mechanisms is crucial for public health.

Purpose of the Study:

  • To investigate the induction of c-fos proto-oncogene expression in the rat brain by various convulsants.
  • To determine if c-fos mRNA distribution can serve as a marker for neurotoxic action.
  • To examine the effects of lindane isomers and GABAA-receptor antagonists on c-fos expression.

Main Methods:

  • In situ hybridization was used to detect c-fos mRNA in rat brain tissue.
  • Administration of gamma-hexachlorocyclohexane (lindane), alpha-HCH, delta-HCH, pentylenetetrazole (PTZ), and picrotoxin (PTX).
  • Dose-dependent effects of lindane on c-fos expression were analyzed.

Main Results:

  • Lindane induced c-fos expression in a dose-dependent manner, particularly in cortical and hippocampal areas.
  • Non-convulsant lindane isomers (alpha- and delta-HCH) did not induce c-fos but blocked lindane-induced expression.
  • PTZ and PTX induced c-fos expression, but with distinct spatial patterns.

Conclusions:

  • The distribution of c-fos mRNA following exposure to toxicants can indicate neurotoxic effects.
  • Lindane and GABAA-receptor antagonists modulate c-fos expression in the rat brain.
  • c-fos mRNA serves as a valuable biomarker for assessing neurotoxicity.

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