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

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.

journal_name

Behav Brain Res

authors

Billauer-Haimovitch H,Slotkin TA,Dotan S,Langford R,Pinkas A,Yanai J

doi

10.1016/j.bbr.2009.08.006

subject

Has Abstract

pub_date

2009-12-28 00:00:00

pages

499-504

issue

2

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(09)00473-2

journal_volume

205

pub_type

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