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Related Experiment Videos

Additional repression of activity-dependent c-fos and BDNF mRNA expression by lipophilic compounds accompanying a

Lisa Imamura1, Kaori Kurashina, Tomomi Kawahira

  • 1Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan.

Neurotoxicology
|November 6, 2004
PubMed
Summary

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Environmental disruptors (EDs) can harm neonatal brain development. This study shows that even at low doses, combined EDs like DDT, DES, and bisphenol A additively repress gene expression and calcium uptake in developing brain cells.

Area of Science:

  • Neuroscience
  • Toxicology
  • Developmental Biology

Background:

  • Environmental disruptors (EDs) are lipophilic compounds potentially impacting neonatal brain development.
  • Activity-dependent gene expression (BDNF, c-fos) in cerebellar granule cells (CGCs) relies on calcium (Ca2+) influx.
  • Previous work showed permethrin represses BDNF/c-fos induction and Ca2+ influx in CGCs.

Purpose of the Study:

  • To investigate if other lipophilic EDs affect Ca2+ signal-induced gene expression like permethrin.
  • To determine if these effects are synergistic or additive.

Main Methods:

  • Primary mouse cerebellar granule cells (CGCs) were used.
  • Cells were pretreated with p,p'-DDT, diethylstilbestrol (DES), or bisphenol A.
  • Gene expression (c-fos, BDNF mRNA) and Ca2+ uptake were measured after exposure.

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Main Results:

  • p,p'-DDT, DES, and bisphenol A dose-dependently repressed gene induction and Ca2+ uptake in CGCs.
  • Simultaneous exposure with permethrin showed additive repression on gene induction and Ca2+ uptake.
  • These effects occurred at non-toxic concentrations.

Conclusions:

  • Lipophilic EDs can interfere with crucial Ca2+ signaling pathways in developing neurons.
  • The combined exposure to multiple EDs may lead to additive neurodevelopmental toxicity.
  • Even low-dose environmental exposures warrant concern for potential brain development disruption.