Perinatal diesel exhaust exposure causes persistent changes in the brains of aged mice: An assessment of behavioral and biochemical endpoints related to neurodegenerative disease

Abstract

AbstractEpidemiological studies support an association between air pollution exposure, specifically particulate matter (PM), and neurodegenerative disease. Diesel exhaust (DE) is a principal component of ambient air pollution and a major contributor of PM. Our study aimed to examine whether early‐life perinatal DE exposure is sufficient to affect behavioral and biochemical endpoints related to Alzheimer's disease later in life. To achieve this, mice were perinatally exposed (embryonic day 0–postnatal day 21) to DE (250–300 μg/m3) or filtered air (FA), and allowed to reach aged status (>18 months). Mice underwent behavioral assessment at 6 and 20 months of age, with tissue collected at 22 months for biochemical endpoints. At 6 months, minimal changes were noted in home‐cage behavior of DE treated animals. At 20 months, an alternation deficit was noted with the T‐maze, although no difference was seen in the object location task or any home‐cage metrics. DE exposure did not alter the expression of Aβ42, phosphorylated tau S199, or total tau. However, IBA‐1 protein, a microglial activation marker, was significantly higher in DE exposed animals. Further, lipid peroxidation levels were significantly higher in the DE exposed animals compared to FA controls. Cytokine levels were largely unchanged with DE exposure, suggesting a lack of inflammation despite persistent lipid peroxidation. Taken together, the findings of this study support that perinatal exposure alone is sufficient to cause lasting changes in the brain, although the effects appear to be less striking than those previously reported in younger animals, suggesting some effects do not persist over time. These findings are encouraging from a public health standpoint and support the aggressive reduction of DE emissions to reduce lifetime exposure and potentially reduce disease outcome.