Prenatal Exposure to Urban Air Nanoparticles in Mice Causes Altered Neuronal Differentiation and Depression-Like Responses

Abstract

Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM). In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m3) or control filtered ambient air for 10 weeks (3×5 hour exposures per week), encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml) to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.

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

“…In children, various components of air pollution have been associated with impaired cognitive abilities [11,12], deficits in attention-related behaviors [13-15], reduced mental development index and IQ scores [16], symptoms of anxiety/depression [17,18], decreased nonverbal reasoning ability [19] and delayed psychomotor development [20]. Animal models confirm behavioral and CNS toxicity in response to gestational, postnatal and adult exposures to air pollution and/or its components [10], including findings of depressive-like behaviors, impaired spatial learning and memory, reduced apical dendritic spine density and dendritic branching in hippocampus [21], reduced numbers of hippocampal neuronal GluA1glutamate receptor subunits and altered neuronal differentiation of cortical neurons [22] and altered locomotor activity and levels of brain catecholamines [23]. …”

“…Hyperglutamate function has been hypothesized to underlie ASD [71], and air pollution impacts brain glutamate function [22]. Both developing and adult microglia have functional glutamate receptors and microglial activation can engender glutamate release [72,73].…”

Uneven Futures of Human Lifespans: Reckonings from Gompertz Mortality Rates, Climate Change, and Air Pollution

“…In vitro, nPM rapidly induced the free radical nitric oxide (NO) with ensuing nitrosylation of glutamate receptors [46]. Moreover, gestational exposure of rats to nPM impaired postnatal neuronal differentiation and increased adult depressive behaviors [47]. Although our exposure model did not alter rodent birth weight, the International Collaboration of Air pollution and Pregnancy Outcomes (ICAPPO) observed associations of PM10 with lower birth weight (-8.9 gm per 10 ug/m 3 of PM10)[48].…”

Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

“…Several epidemiological and rodent studies have demonstrated a correlation between exposures during gestation or early development and increased risk for developing psychiatric disorders (Hellemans et al, 2010; Davis et al, 2013; Talati et al, 2013); indeed, arsenic exposure has been associated with depression in epidemiological studies (Zierold et al, 2004). While it is unclear if the damage resulting from developmental exposures is amenable to intervention, we have provided evidence that arsenic-induced deficits can be reversed with fluoxetine treatment.…”