Maternal Stress and Effects of Prenatal Air Pollution on Offspring Mental Health Outcomes in Mice

Abstract

Background: Low socioeconomic status is consistently associated with reduced physical and mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown.Objectives: We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neurocognitive disorders in adulthood.Methods: Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation.Results: Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased proinflammatory interleukin (IL)-1β levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1.Conclusions: These results show that maternal stress during late gestation increases the susceptibility of offspring—particularly males—to the deleterious effects of prenatal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain.Citation: Bolton JL, Huff NC, Smith SH, Mason SN, Foster WM, Auten RL, Bilbo SD. 2013. Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice. Environ Health Perspect 121:1075–1082; http://dx.doi.org/10.1289/ehp.1306560

<i>In utero</i> exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus

“…They also found that the same behavior was observed in rats with raphe nucleus damage. In addition, male offspring of dams that experienced both PM exposure and nest material restriction (stress) displayed increased anxiety (Bolton et al, 2013). The results of the present study are compatible with, and supported by, those of the previous studies.…”

“…In particular, epidemiological studies suggested that pre-and post-natal exposure to traffic air pollutants, including high concentrations of particulate matter (PM), could increase susceptibility for the onset of neurodevelopmental disorders (Becerra et al, 2013;Kalkbrenner et al, 2015). Animal research also demonstrated that in utero exposure to both PM and stress induced anxietylike behavior and impaired cognition of male offspring (Bolton et al, 2013).…”

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…The consequences of early-life (prenatal as well as postnatal) stress on emotional and social behaviors have been a subject of several recent reviews (eg, Sandi and Haller, 2015;Nishi et al, 2014). Here, we summarize in Table form the consequences of chronic early-life adversity provoked by abnormal maternal care in the limited bedding-nesting environment (Gilles et al, 1996;Molet et al, 2014), a model recently adopted and adapted by over 50 laboratories around the world (eg, Raineki et al, 2010;Wang et al, 2011;Bolton et al, 2013;Machado et al, 2013;Maniam et al, 2014;Kohl et al, 2015;Naninck et al, 2015; Table 1). …”

Exposition aux gaz d’échappement diesel durant la gestation : quelles conséquences sur le développement foeto-placentaire ? Apport des modèles animaux

“…La dégradation de la qualité de l'alimentation dans les pays déve-loppé et la contamination de notre environnement par des perturbateurs endocriniens sont les facteurs les plus souvent incriminés pour comprendre l'épidémie actuelle d'obésité et de maladies métaboliques. Cependant, l'exposition chronique à la pollution atmosphérique pourrait aussi jouer un rôle, comme le suggère en particulier une étude chez la souris qui montre que l'exposition foetale à des gaz d'échappement diesel augmente la réponse post-natale à un régime obésogène, avec des effets qui varient selon le sexe de l'individu (Bolton et al 2012, Bolton et al 2013). …”