| Maternal Stress Modulates the Effects of Developmental Lead Exposure Deborah A. Cory-Slechta, Miriam B. Virgolini, Mona Thiruchelvam, Doug D. Weston, and Mark R. Bauter Department of Environmental Medicine and National Institute of Environmental Health Environmental Health Sciences Center, University of Rochester Medical School, Rochester, New York, USA 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 schedule-controlled 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. Key words: corticosterone, dopamine, frontal cortex, lead, nucleus accumbens, stress, striatum. Environ Health Perspect 112:717-730 (2004) . doi:10.1289/ehp.6481 available via http://dx.doi.org/ [Online 29 January 2004]
Address correspondence to D.A. Cory-Slechta, Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd., Piscataway, NJ 08854 USA. Telephone: (732) 445-0200. Fax: (732) 445-0131. E-mail: dcs@eohsi.rutgers.edu This work was supported in part by grants ES01247, ES05903, and ES05017 from the National Institute of Environmental Health Sciences. The authors declare they have no competing financial interests. Received 27 May 2003 ; accepted 27 January 2004.
The full version of this article is available for free in HTML or PDF formats. |
