TY - JOUR
T1 - Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by nicotine administration and neural stem cell transplantation
AU - Billauer-Haimovitch, Hana
AU - Slotkin, Theodore A.
AU - Dotan, Sharon
AU - Langford, Rachel
AU - Pinkas, Adi
AU - Yanai, Joseph
N1 - Funding Information:
Supported by grants from The United States-Israel Binational Science Foundation BSF2005003 and NIH ES014258 .
PY - 2009/12/28
Y1 - 2009/12/28
N2 - 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.
AB - 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.
KW - Chlorpyrifos
KW - Mice
KW - Morris maze testing
KW - Neural stem cell therapy
KW - Neurobehavioral teratogenicity
KW - Nicotine therapy
KW - Prenatal exposure
UR - http://www.scopus.com/inward/record.url?scp=70349769163&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349769163&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2009.08.006
DO - 10.1016/j.bbr.2009.08.006
M3 - Article
C2 - 19682500
AN - SCOPUS:70349769163
SN - 0166-4328
VL - 205
SP - 499
EP - 504
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -