Maternal stress modulates the effects of developmental lead exposure.

Abstract

Lead exposure is higher among children with low socioeconomic status (SES) compared with other children in the United States. Low SES itself is a known risk factor for various diseases and dysfunctions, effects that have been ascribed to chronic stress and associated elevation of glucocorticoids. Chronically elevated glucocorticoids and Pb provoke similar behavioral changes, and both can act on mesocorticolimbic systems of the brain. In this study we examined the hypothesis that these co-occurring risk factors, Pb and environmental stress, would interact and modulate each others' effects. Using a rodent model, we focused on the specific contributions of maternal stress (restraint) and maternal Pb exposure (150 ppm in drinking water) on corticosterone levels of offspring, as well as on neurotransmitter changes and a behavioral baseline (fixed-interval schedulecontrolled performance) with known sensitivities to Pb. We observed interactions of Pb and stress that differed in relation to outcome measure and sex. In addition, potentiated effects (effects of Pb plus stress but showing no changes produced by either alone) were observed more frequently in females. Importantly, Pb alone (in males) and Pb plus stress (in females) permanently elevated corticosterone levels in offspring; even short-term Pb exposure to dams could cause this effect. Such increases could suggest a potential new mechanism by which Pb exposure could directly or indirectly enhance susceptibility to diseases and dysfunctions and induce cognitive deficits. Moreover, the interactive effects of Pb and stress, and particularly the potentiated effects of Pb plus stress, raise questions about whether current risk assessment strategies sufficiently consider the potential for modulation of toxicity that can accrue from intercurrent risk factors.

Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort

“…For example, studies have shown that maternal stressors, such as restraint stress, synergistically interact with diesel exhaust (Bolton et al 2013) and lead (Cory-Slechta et al 2004) to produce more profound effects in the offspring of pregnant rodents than either exposure alone. These relationships varied by offspring sex.…”

“…Adult male offspring demonstrated anxiety, significant memory deficits, and an increased neuroinflammatory response in the brain (e.g., decreased IL-10 levels) when co-exposed to diesel exhaust and stress during late pregnancy; female offspring of co-exposed dams showed only a slight increase in anxiety (Bolton et al 2013). Co-exposure to stress and prenatal lead was associated with changes in dopamine and corticosterone levels in female offspring in adulthood; in males, these exposures corresponded to increased impulsive choice behaviors (Cory-Slechta et al 2004). In the only study of stress as a modifier of pesticide exposure, Levin et al demonstrated that when maternal rat dams were stimulated with dexamethasone during gestation to elicit a stress response and offspring were exposed to chlorpyrifos, an OP pesticide, shortly after birth, the co-exposed offspring presented with greater hyperactivity, longer latency to begin feeding, and shorter feeding duration at 4–10 weeks after birth (adolescence and adulthood) compared to controls and to offspring exposed to chlorpyrifos alone.…”

Lead and cognitive function in adults: A questions and answers approach to a review of the evidence for cause, treatment, and prevention

“…One study has reported that environmental enrichment reversed the cognitive and molecular deficits induced by developmental lead exposure in rats (Guilarte, Toscano, McGlothan, & Weaver, 2003). Other studies have evaluated the interaction between 'environmental stress' and lead exposure on behavioural outcomes in rodents (Cory-Slechta, Virgolini, Thiruchelvam, Weston, & Bauter, 2004;Virgolini, Bauter, Weston, & Cory-Slechta, 2006;Virgolini et al, 2005;Virgolini, Volosin, Fulginiti, & Cancela, 2004). Finally, we have observed in the BMS that living in a neighbourhood with higher levels of psychosocial hazards (methods for neighbourhood psychosocial hazards scale in Glass et al, 2006) interacted with cumulative lead dose in associations with cognitive dysfunction.…”

Application of fluorescent protein-tagged trans factors and immobilized cis elements to monitoring of toxic metals based on in vitro protein–DNA interactions

“…Long-term exposure to metals such as arsenic, cadmium, mercury, and lead by taking polluted water and foods increases a risk of chronic diseases (Cory-Slechta et al, 2004). Development of respiratory disorders, skin lesions, and carcinomata caused by arsenic poisoning is a well-known example to explain such risk (Bagla and Kaiser, 1996;Nordstrom, 2002).…”