Effects of early life exposure to traffic-related air pollution on brain development in juvenile Sprague-Dawley rats

Abstract

Epidemiological studies link traffic-related air pollution (TRAP) to increased risk for various neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship between TRAP and adverse neurodevelopmental outcomes. Moreover, much of the preclinical literature reports effects of concentrated ambient particles or diesel exhaust that do not recapitulate the complexity of real-world TRAP exposures. To assess the developmental neurotoxicity of more realistic TRAP exposures, we exposed male and female rats during gestation and early postnatal development to TRAP drawn directly from a traffic tunnel in Northern California and delivered to animals in real-time. We compared NDD-relevant neuropathological outcomes at postnatal days 51-55 in TRAPexposed animals versus control subjects exposed to filtered air. As indicated by immunohistochemical analyses, TRAP significantly increased microglial infiltration in the CA1 hippocampus, but decreased astrogliosis in the dentate gyrus. TRAP exposure had no persistent effect on pro-inflammatory cytokine levels in the male or female brain, but did significantly elevate the anti-inflammatory cytokine IL-10 in females. In male rats, TRAP significantly increased hippocampal neurogenesis, while in females, TRAP increased granule cell layer width. TRAP had no effect on apoptosis in either sex. Magnetic resonance imaging revealed that TRAP-exposed females, but not males, also exhibited decreased lateral ventricular volume, which was correlated with increased granule cell layer width in the hippocampus in females. Collectively, these data indicate that exposure to real-world levels of TRAP during gestation and early postnatal development modulate neurodevelopment, corroborating epidemiological evidence of an association between TRAP exposure and increased risk of NDDs.

The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer’s Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats

“…2020 ; Edwards et al. 2020 ; Patten et al. 2020 ), was maintained under controlled environmental conditions (20°–26°C, 12:12 light:dark cycle) with food (Envigo Global 18% Protein Rodent Diet) and tap water provided ad libitum .…”

“…After washes in PBS, blocks were sunk in 30% wt/vol sucrose (ThermoFisher Scientific) in PBS for 1 wk, before being embedded in Optimal Cutting Temperature (OCT) compound (ThermoFisher Scientific) and flash frozen in a bath of dry ice and methanol. Cryosections thick were obtained from frozen PFA-fixed brain blocks as previously described ( Patten et al. 2020 ).…”

“…2020 ). For each animal, three or four sections from the dorsal hippocampus (Bregma to ; confirmed using a photographic atlas of the rat brain) were immunostained as previously described ( Patten et al. 2020 ) using the antibodies described in Table S1.…”

Pathological Cardiopulmonary Evaluation of Rats Chronically Exposed to Traffic-Related Air Pollution

“…The tunnel vivarium, adjacent to a heavily trafficked freeway tunnel in Northern California, continuously drafted air from the eastbound exit of the tunnel bores with an air flow rate of in each chamber ( Berg et al. 2020 ; Patten et al. 2020 ).…”

Developmental exposure to near roadway pollution produces behavioral phenotypes relevant to neurodevelopmental disorders in juvenile rats

“…Importantly, we also discovered that both roadside-reared groups, TRAP and filtered air (FA), with exposure to the same noise and vibrational stress, had significantly delayed growth and development of psychomotor reflexes, displayed altered social interactions, and exhibited abnormal motor activity. Histological outcomes from these exposures are described in our companion manuscript 45 . Further, we found no evidence for an effect, due to stress or otherwise, of the pregnant dams' transport to the roadside facility on offspring behavior.…”