Over the past year, the scientists here at the Duke Superfund Research Center have been busy trying to better understand how certain chemicals may impact health when people are exposed to them at critical points in time. Below are summaries from a couple of papers they’ve published in scientific, peer-reviewed journals in the last year.
Slotkin, Theodore A., et al. “Prenatal dexamethasone augments the sex-selective developmental neurotoxicity of chlorpyrifos: Implications for vulnerability after pharmacotherapy for preterm labor.” Neurotoxicology and teratology 37 (2013): 1-12.
This study explored whether prenatal exposures to drugs or chemicals that, by themselves, affect brain development are also able to sensitize an individual to neurotoxicants encountered later in life. The two chemicals studied were dexamethasone, which is a glucocorticoid drug given to manage preterm labor, and chlorpyrifos (CPF), a widely-used organophosphate pesticide to which virtually everyone is exposed. Previous research has shown that male and female rat brains are affected very differently by early-life exposure to chlorpyrifos: typically, the male brain is more sensitive than is the female. The study focused on serotonin, a neurotransmitter highly involved in emotional behaviors. Results show:
Sex differences in the effects of CPF alone:
- Males showed deficits in serotonergic impulse activity, resulting in a compensatory upregulation of serotonin receptors
- The female brain was spared most of these effects, showing that it is better able to rebound after exposure to CPF than the male brain.
Prenatal dexamethasone + chlorpyrifos:
- In males, prior exposure to dexamethasone worsened the suppression of impulse activity while also impairing the compensatory elevation of receptors. Accordingly, there is a greater overall impairment of synaptic function in the animals receiving the two treatments as compared to either one alone.
- In females, the dual exposure removed the “protection” seen for exposure to chlorpyrifos alone, rendering them as vulnerable as the males
The results indicate that prenatal exposures to glucocorticoids are likely to create a subpopulation with heightened vulnerability to the effects of environmental neurotoxicants encountered later in life. This is critically important because approximately 10% of all babies born in the US are exposed to prenatal glucocorticoid therapy, and also because endogenous, circulating glucocorticoids are elevated by maternal stress.
Levin, Edward D., et al. “Prenatal dexamethasone augments the neurobehavioral teratology of chlorpyrifos: Significance for maternal stress and preterm labor.” Neurotoxicology and teratology 41 (2014): 35-42.
The objective of this study, which was designed based on the premise that exposure to a drug or chemical during early development may sensitize an individual to later exposure to an unrelated toxicant, was to determine if prenatal exposure to glucocorticoids, which have previously been shown to produce neurodevelopmental disorders in children, and later exposure to chlorpyrifos had neurobehavioral effects in rats. To do this, both male and female rats were treated with either chlorpyrifos and dexamethasone individually or in combination and later performed tests measuring exploratory behavior, locomotor activity, novel environment behavior, and novel object recognition.
- For tests measuring locomotor activity, novelty-suppressed feeding, and novel object recognition, researchers found that chlorpyrifos or dexamethasone alone had small, often non-significant effects that were in the same direction. However, for the same set of tests, exposure to dexamethasone and chlorpyrifos produced larger, significant effects that may be additive.
- When rats performed tests measuring habituation behavior after being treated with chlorpyrifos or dexamethasone alone, the effects were in opposite directions or were restricted to only one chemical. However, when rats were treated with chlorpyrifos following exposure to dexamethasone, the effects on habituation behavior were enhanced.
- Additionally, this combined treatment also enhanced the effects of chlorpyrifos by eliminating or reversing normal sex-differences in behavior.
This study is important for two reasons, 1) it shows that combined exposures can cause not only long-term neurochemical changes, but also long-term functional behavioral impairments, and 2) while an individual’s genetic make-up is influential in determining susceptibility, one’s “chemical history” is also an important factor.
