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Alteration of gene expression of G protein-coupled receptors in endocrine disruptors-caused hyperactive rats

Masami Ishido1, Masatoshi Morita, Syuichi Oka

  • 1Endocrine Disruptors and Dioxin Research Projects, National Institute for Environmental Studies, Tsukuba 305-8506, Japan. ishidou@nies.go.jp

Regulatory Peptides
|December 29, 2004
PubMed

Insights

Exposure to endocrine disruptors like BPA and phthalates caused hyperactivity in rats. These chemicals altered gene expression in brain pathways, impacting neurotransmitter systems.

Area of Science:

  • Environmental toxicology
  • Neuroendocrinology
  • Developmental toxicology

Background:

  • Endocrine disruptors are chemicals that can interfere with the body's endocrine system.
  • Exposure during critical developmental periods may have long-lasting effects on behavior and neurobiology.
  • Specific endocrine disruptors have been linked to various health concerns, but their precise neurobehavioral impacts require further elucidation.

Purpose of the Study:

  • To investigate the behavioral and cellular effects of specific endocrine disruptors in developing male Wistar rats.
  • To determine if early-life exposure to endocrine disruptors leads to altered neurochemical pathways and behavioral changes later in life.

Main Methods:

  • Single intracisternal administration of endocrine disruptors (BPA, p-octylphenol, nonylphenol, DBP, DCHP, DEHP) to 5-day-old rats.
  • Behavioral testing for hyperactivity at 4-5 weeks of age.
  • DNA macroarray analysis of midbrain gene expression at 8 weeks.
  • Immunohistochemical analysis of tyrosine hydroxylase in the substantia nigra.

Main Results:

  • Endocrine disruptor exposure resulted in significant hyperactivity in rats during the nocturnal phase.
  • Gene expression analysis revealed alterations in G protein-coupled receptors involved in dopaminergic and peptidergic neurotransduction.
  • Specific changes included decreased dopamine receptor D1A, increased dopamine receptor D2, and downregulated galanin receptor 2 expression.
  • Dopamine transporter gene expression was significantly decreased by some disruptors.
  • Immunohistochemistry showed impaired tyrosine hydroxylase immunoreactivity in the substantia nigra following p-octylphenol exposure.

Conclusions:

  • Early-life exposure to endocrine disruptors induces hyperactivity in rats.
  • These effects are associated with significant alterations in the gene expression of key neurotransmitter systems, including dopaminergic and peptidergic pathways.
  • Endocrine disruptors likely impact both gene expression and protein levels within these critical neurobiological systems.

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