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, 122 (9), 939-45

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


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

Joshua L Allen et al. Environ Health Perspect.


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.

Conflict of interest statement

The authors declare they have no actual or potential competing financial interests.


Figure 1
Figure 1
Mean particle counts and particle mass concentration for each day of exposure. Inset: mean diameter for each day of exposure. Error bars represent SDs.
Figure 2
Figure 2
Images of lateral ventricle from air-exposed (A,C) and CAPS-exposed (B,D) male mice at PND14 (A,B) or at approximately PND270 (C,D). Bars = 10 μm. Quantification of lateral ventricle on PNDs 14 and 55 (E) and PND270 (F). The aqueduct of Sylvius area is shown for PNDs 14 and 55 (E). Data reported as group mean area ± SE. TX, main effect of CAPs treatment. n = 5 animals/sex/treatment/time point. *< 0.05, by two-tailed t-test.
Figure 3
Figure 3
Representative images of GFAP immunoreactivity in the corpus callosum and hippocampus of air- and CAPs-exposed male (A) and female (B) mice at PND14, with (C) relative quantification of GFAP in those regions and in the dentate gyrus, cortex, midbrain, striatum, and anterior commissure immediately adjacent. (D) Representative images of IBA-1 immunoreactivity in the hippocampus and corpus callosum of male mice at PND55. (E) Relative quantification of IBA-1 immunoreactivity in the anterior commissure at PND14 and hippocampus of male mice at PND55. Data reported as percent sex-specific control by time point ± SE. Abbreviations: TX, main effect of CAPs treatment; TP × TX, statistical interaction between CAPs treatment and time point. Bar = 50 μm. n = 5 animals/sex/treatment /time point. *< 0.05, compared with time point– and sex-specific control, by two-tailed t-test.

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