Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by nicotine administration and neural stem cell transplantation

Hana Billauer-Haimovitch, Theodore A. Slotkin, Sharon Dotan, Rachel Langford, Adi Pinkas, Joseph Yanai

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Identifying the mechanisms underlying the adverse effects of developmental neurotoxicants enables the design of therapies that can potentially reverse neurobehavioral deficits in adulthood. We administered chlorpyrifos (CPF), a model organophosphate pesticide to pregnant mice and identified visuospatial deficits in adult offspring using performance in the Morris maze. We then evaluated two strategies to reverse the effects, nicotine administration and transplantation of neural stem cells. Daily administration of nicotine prior to behavioral testing did not alter maze performance by itself, but completely reversed the deficits evoked by prenatal CPF exposure. Similarly, control animals grafted with neural stem cells in adolescence did not show any alterations in behavioral performance as adults, but the grafts completely reversed the effects of prenatal CPF treatment. This study thus provides a model for the development and application of both pharmacologic and cell-based therapies to offset the effects of neurobehavioral teratogens.

Original languageEnglish (US)
Pages (from-to)499-504
Number of pages6
JournalBehavioural Brain Research
Volume205
Issue number2
DOIs
StatePublished - Dec 28 2009
Externally publishedYes

Keywords

  • Chlorpyrifos
  • Mice
  • Morris maze testing
  • Neural stem cell therapy
  • Neurobehavioral teratogenicity
  • Nicotine therapy
  • Prenatal exposure

ASJC Scopus subject areas

  • Behavioral Neuroscience

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