IFEC   20925
INSTITUTO DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Unidad Ejecutora - UE
artículos
Título:
CNS Effects of Developmental Pb Exposure are Enhanced by Combined Maternal and Offspring Stress
Autor/es:
4. VIRGOLINI, M.B.; ROSSI-GEORGE, A; LISEK, R.;WESTON, D.D.; THIRUCHELVAM, M.; CORY-SLECHTA, D.A
Revista:
NEUROTOXICOLOGY
Referencias:
Año: 2008
ISSN:
0161-813X
Resumen:
Lead (Pb) exposure and elevated stress are co-occurring risk factors. Both impact brainmesolimbic dopamine/glutamate systems involved in cognitive functions. We previously foundthat maternal stress can potentiate Pb-related adverse effects in offspring at blood Pb levelsaveraging approximately 40 ug/dl. The current study of combined Pb exposure and stresssought to extend those results to lower levels of Pb exposure, and to examine relationshipsamong consequences in offspring for Fixed Interval (FI) schedule-controlled behavior,neurochemistry and corticosterone levels. Dams were exposed to maternal Pb beginning 2 mosprior to breeding (0, 50 or 150 ppm in drinking water), maternal restraint stress on gestationaldays 16 and 17 (MS), or the combination. In addition, a subset of offspring from each resultanttreatment group was also exposed intermittently to variable stressors as adults (MS+OS).Marked “Pb-stress”-related increases in response rates on a Fixed Interval schedule, abehavioral performance with demonstrated sensitivity to Pb, occurred preferentially in femaleoffspring even at mean blood Pb levels of 11 ug/dl when 50 ppm Pb was combined withmaternal and offspring stress. Greater sensitivity of females to frontal cortex catecholaminechanges may contribute to the elevated FI response rates as mesocorticolimbic systems arecritical to the mediation of this behavior. Basal and final corticosterone levels of offspring usedto evaluate FI performance differed significantly from those of non-behaviorally tested (NFI)littermates, demonstrating that purported mechanisms of Pb, stress or Pb/stress effectsdetermined in non-behaviorally trained animals cannot necessarily be generalized to animalswith behavioral histories. Finally, the persistent and permanent consequences of Pb, stress andPb+stress in offspring of both genders suggest that Pb screening programs should includepregnant women at risk for elevated Pb exposure, and that stress should be considered as anadditional risk factor. Pb+stress effects observed in the absence of either risk factor alone (i.e.,potentiated effects) raise questions about the capacity of current hazard identificationapproaches to adequately identify human health risks posed by neurotoxicants.