Environmental and Social Toxins and the Developmental Origins of Disease

It is increasingly evident that diverse genes and environmental exposures combine or synergize to produce a spectrum of health outcomes later in life dependent upon critical developmental windows. For instance, multiple prenatal/maternal environmental toxins have been linked to autism spectrum disorder (ASD), but the associations of single agents have been relatively weak. This suggests it is the combination of multiple maternal exposures that increases vulnerability in offspring. We now recognize that non-chemical stressors, such as limited resources or social support of the mother, can increase vulnerability of the fetus to chemical stressor exposures (e.g., pollution or toxins), which could explain why a single exposure or risk factor in isolation is a modest predictor of autism risk. To explore these issues I developed a new rodent model that employs the combined effects of an ethologically relevant maternal stressor and environmentally relevant pollutant, diesel exhaust, both of which have been implicated in autism. We have shown that maternal diesel exhaust particle (DEP) exposure combined with maternal stress (MS) (but neither in isolation) produces early-life communication deficits, and long-term social, cognitive, and emotional deficits in male but not female offspring. Conversely, females show increased depressive-like behavior in adulthood. We have also shown that DEP exposure significantly alters microglial colonization of the male but not female embryonic brain, and combined prenatal DEP and MS exposure leads to persistent changes in the function of microglia of the same brain regions of males.

 Representative Publications:

  1. Bolton JL, Smith SH, Huff NC, Gilmour MI, Foster WM, Auten RL, Bilbo SD.  Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner.  FASEB J, 2012; 26(11):4743-54. PMCID Exempt
  2. Bolton JL, Huff NC, Smith SH, Mason SN, Foster WM, Auten RL, Bilbo SD. Maternal stress worsens effects of prenatal air pollution on offspring mental health outcomes.  EHP, 2013; 121(9):1075-82. PMCID:PMC3764088
  3. Bolton JL, Auten RL, Bilbo SD. Prenatal Air Pollution Exposure Induces Sexually Dimorphic Fetal Programming of Metabolic and Neuroinflammatory Outcomes in Adult Offspring. Brain Behav Immun, 2014; 37:30-44.PMCID Exempt
  4. Bolton JL, Marinero S, Hassanzadeh T, Natesan D, Le D, Belliveau C, Mason SN, Auten RL, Bilbo SD. Gestational exposure to air pollution alters cortical volume, microglial morphology, and microglia-neuron interactions in a sex-specific manner.  Frontiers in Synaptic Neuroscience, 2017, 31:10. PMCID:PMC5449437