Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice

Abstract

Background: Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression.Objectives: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development.Methods: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4–7 and 10–13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified.Results: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males.Conclusions: We observed brain region– and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans.Citation: Allen JL, Liu X, Pelkowski S, Palmer B, Conrad K, Oberdörster G, Weston D, Mayer-Pröschel M, Cory-Slechta DA. 2014. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice. Environ Health Perspect 122:939–945; http://dx.doi.org/10.1289/ehp.1307984

Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders

“…As previously reported [80], mean particle diameter for these exposures was consistently below 100 nm; mean CAPS counts across the 8 days of exposures was approximately 200,000 particles/cm 3 , and the mean particle mass concentration was 96 μg/m 3 . These values are similar to values reported for expressway traffic in L. A.…”

Role of astrocyte activation in fine particulate matter-enhancement of existing ischemic stroke in Sprague-Dawley male rats

“…In the present study, PM 2.5 exposure did not induce marked changes in GFAP in male rat brain. The findings in this study differ from those of Allen et al (2014) with respect to GFAP expression, possibly due to factors such as age, experimental PM administration, and species. Lucchini et al (2012) demonstrated that children were more sensitive to PM than adults, which may account for the findings noted by Allen et al (2014).…”

“…One of the prominent pathological features of IS is reactive astrocytes, characterized by changes in morphology and upregulation of GFAP, and finally forming glial scars (Choudhury and Ding, 2015). Allen et al (2014) reported that early postnatal exposure to inhalation PM 2.5 at 10-fold the concentration in ambient air in male C57BL6/J mice decreased GFAP immunoreaction at postnatal day (PND) 14 and PND 55, whereas an increased GFAP expression was noted at PND14 in the female mouse brain. In the present study, PM 2.5 exposure did not induce marked changes in GFAP in male rat brain.…”

Sex-specific differences in fetal growth in newborns exposed prenatally to traffic-related air pollution in the PELAGIE mother–child cohort (Brittany, France)

“…There is growing evidence that air pollution may have a neurotoxic effect at early stages of development (Genc et al, 2012) even in newborns with appropriate fetal growth. Neuroinflammation, oxidative stress, and glial activation have been identified as potential mechanisms by which air pollution may impair the central nervous system (Calderón-Garcidueñas et al, 2012;Block and Calderón-Garcidueñas, 2009;Allen et al, 2014). Neuroinflammation prompted by a fetal inflammatory response syndrome can damage the fetal brain and increase the risk of ventriculomegaly in fetuses and newborns (Korzeniewski et al, 2014), itself associated with larger HC and total brain volume during pregnancy (Roza et al, 2008).…”