Interactions of Chronic Lead Exposure and Intermittent Stress: Consequences for Brain Catecholamine Systems and Associated Behaviors and HPA Axis Function

Virgolini, Miriam Beatríz; Chen, Kevin; Weston, D.; Bauter, Mark R.; Cory‐Slechta, Deborah A.

doi:10.1093/toxsci/kfi269

Cited by 105 publications

(85 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Supernatant was collected to measure catecholamine, 5-HT and 5-HIAA levels using a high-performance liquid chromatography (HPLC) system with electrochemical detector as previously described Virgolini et al 2005;Virgolini et al 2006). The resulting pellets were digested in 1 ml of 0.5 N NaOH for measurements of protein concentration using Bio-Rad assay reagents.…”

Section: Neurochemical Determinations Of Catecholamines 5-ht and 5-hiaamentioning

confidence: 99%

CNS effects of developmental Pb exposure are enhanced by combined maternal and offspring stress

et al. 2008

View full text Add to dashboard Cite

Lead (Pb) exposure and elevated stress are co-occurring risk factors. Both impact brain mesolimbic dopamine/glutamate systems involved in cognitive functions. We previously found that maternal stress can potentiate Pb-related adverse effects in offspring at blood Pb levels averaging approximately 40 ug/dl. The current study of combined Pb exposure and stress sought to extend those results to lower levels of Pb exposure, and to examine relationships among consequences in offspring for Fixed Interval (FI) schedule-controlled behavior, neurochemistry and corticosterone levels. Dams were exposed to maternal Pb beginning 2 mos prior to breeding (0, 50 or 150 ppm in drinking water), maternal restraint stress on gestational days 16 and 17 (MS), or the combination. In addition, a subset of offspring from each resultant treatment 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, a behavioral performance with demonstrated sensitivity to Pb, occurred preferentially in female offspring even at mean blood Pb levels of 11 ug/dl when 50 ppm Pb was combined with maternal and offspring stress. Greater sensitivity of females to frontal cortex catecholamine changes may contribute to the elevated FI response rates as mesocorticolimbic systems are critical to the mediation of this behavior. Basal and final corticosterone levels of offspring used to evaluate FI performance differed significantly from those of non-behaviorally tested (NFI) littermates, demonstrating that purported mechanisms of Pb, stress or Pb/stress effects determined in nonbehaviorally trained animals cannot necessarily be generalized to animals with behavioral histories. Finally, the persistent and permanent consequences of Pb, stress and Pb+stress in offspring of both genders suggest that Pb screening programs should include pregnant women at risk for elevated Pb exposure, and that stress should be considered as an additional 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 identification approaches to adequately identify human health risks posed by neurotoxicants.

show abstract

Section: Neurochemical Determinations Of Catecholamines 5-ht and 5-hiaamentioning

confidence: 99%

CNS effects of developmental Pb exposure are enhanced by combined maternal and offspring stress

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The social ecology governing a child's environment can induce permanent changes in brain structure and function that almost certainly modify its vulnerability to toxic exposures (Weiss and Bellinger, 2006). Indeed, animal studies indicate that maternal stress is one determinant of the effects of lead (Cory-Slechta et al, 2004;Virgolini et al, 2005). And, further, the infant and the fetus are exposed to a broth of chemicals from their in utero environment and their mothers' breast milk that is poorly accounted for when assessing the effects of lead (Cory-Slechta, 2005).…”

Section: Costs and Consequences Of Lead Exposurementioning

confidence: 99%

A rationale for lowering the blood lead action level from 10 to 2μg/dL

Gilbert¹,

2006

View full text Add to dashboard Cite

Fifteen years ago, in 1991, the U.S. Centers for Disease Control and Prevention (CDC) established 10 μg/dL as the lowest level of concern for children's blood lead levels. This value is extremely important because, historically, policy makers and public health officials generally have acted to remove sources of lead exposure only after the CDC's level of concern had been exceeded. A growing body of evidence, however, reveals that blood lead levels below 10 μg/dL may impair neurobehavioral development. There is now sufficient and compelling scientific evidence for the CDC to lower the blood lead action level in children. This review argues that a level of 2 μg/dL is a useful and feasible replacement. Although it can be argued, in turn, that no threshold for the health effects of lead is demonstrable, analytically a blood level of 2 μg/dL is readily and accurately measured and provides a benchmark for successful prevention. Lowering the level of concern would encourage and accelerate the investments needed to ensure that children are protected from lead exposure in their homes, schools, and play settings. Such a program would also offer economic advantages because of the coupling between lead, educational attainment, earnings and anti-social conduct. By lowering the blood action level, CDC will promote policies and initiatives designed to further reduce children's exposure to this potent developmental neurotoxicant.

show abstract

“…Stress exacerbates the toxicity of many contaminants (Hougaard and Hansen, 2007;Relyea and Mills, 2001;Verwer et al, 2007), including lead. Maternal stress, induced by novelty, restraint, or cold, modulates the effects of prenatal lead exposure on offspring performance on FI schedule-controlled responding, as well as basal and stress-induced corticosterone response (Cory-Slechta, 2005;Virgolini et al, 2005;Virgolini et al, 2006). In these studies, the effects of combined exposure to lead and stress were detected in the absence of an effect of either factor alone, and the profile of effects of the combined exposure differed notably from the effects of lead alone.…”

Section: Ses As a Modifier Of The Association Between Lead And Childrmentioning

confidence: 99%

Lead neurotoxicity and socioeconomic status: Conceptual and analytical issues

Bellinger

2008

NeuroToxicology

130

View full text Add to dashboard Cite

Socioeconomic status (SES) is usually considered to be a potential confounder of the association between lead exposure and children's neurodevelopment, but experimental and epidemiological data suggest that SES might also modify lead neurotoxicity. The basis of this effect modification is uncertain, but might include differences among SES strata in co-exposures to other neurotoxicants, genetic susceptibilities, environmental enrichment, and stress. The role of SES in the causal nexus is likely to include other dimensions, however. It conveys information about lead exposure opportunities as well as about predictors of child outcome that are correlated with but causally independent of lead. Failure to distinguish these aspects of SES will lead to an underestimate of lead's contribution, and might even result in attributing to SES health effects that should be attributed to lead. Conventional models, which treat SES and SES-related factors solely as potential confounders, do not capture the possibility that a child's early lead exposure alters the behaviors that the child elicits from others. Failure to model lead's contribution to such time-varying covariates will also tend to bias estimates of lead neurotoxicity toward the null. On a transgenerational level, low SES might be a proxy for vulnerability to lead. To estimate the burden of lead-associated neurotoxicity on a population level, we need to apply analytical approaches that model a child's development and its context as a complex system of interdependent relationships that change over time.Socioeconomic status (SES) has played a central role in efforts to characterize the magnitude of the risk that lead poses to children. Because exposure is often greater among children of low SES (Baghurst et al., 1999) and low SES is a powerful predictor of neurodevelopment (Tong et al., 2007), it has long been recognized that due consideration must be given to the possibility that any observed association between lead exposure and neurodevelopment is, in part, an artifact of residual confounding, and thus reflects a Type I error of inference. Indeed, adjusting for SES and related covariates can result in reductions of 50% or more in the magnitude of lead's regression coefficient (e.g., Bellinger et al., 1992). Whether an investigator adequately handled this issue, avoiding a Type I error of inference, became one of the central determinants of whether the inferences drawn from a lead study were viewed as credible.The role of SES in lead studies is likely to be much more complex than that of solely a confounder, however. Two dimensions of this issue are discussed in this paper. The first section summarizes epidemiologic and experimental findings suggesting that SES and SES-related aspects of a child's social environment modify the neurotoxicity of lead such that children of

show abstract

Interactions of Chronic Lead Exposure and Intermittent Stress: Consequences for Brain Catecholamine Systems and Associated Behaviors and HPA Axis Function

Cited by 105 publications

References 36 publications

CNS effects of developmental Pb exposure are enhanced by combined maternal and offspring stress

CNS effects of developmental Pb exposure are enhanced by combined maternal and offspring stress

A rationale for lowering the blood lead action level from 10 to 2μg/dL

Lead neurotoxicity and socioeconomic status: Conceptual and analytical issues

Contact Info

Product

Resources

About