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.
This study sought to investigate the mechanism(s) by which exposure to concentrated ambient ultrafine particles (CAPS) adversely influence central nervous system (CNS) development.
C57Bl6/J mice were exposed to ultrafine (<100 nm) CAPS using the Harvard University Concentrated Ambient Particle System or filtered air postnatal days (PND) 4-7 and 10-13 after which animals were euthanized either 24 hours or 40 days following cessation of exposure, and in another group of males at 270 days (ventricle area). Lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified.
CAPS induced ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice that persisted through young adulthood. Additionally, CAPS-exposed males generally showed decreases in developmentally important CNS cytokines, whereas, in females, CAPS induced a neuroinflammatory response as indicated by increases in CNS cytokines. CAPS also induced changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increases hippocampal glutamate in males.
CAPS induces brain region- and sex-dependent alterations in cytokines and neurotransmitters in both males and females. Lateral ventricle dilation (i.e., ventriculomegaly) is only observed 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 outcome in humans.