Diesel exhaust particles induced inflammatory responses are associated with executive functions deficits in juvenile mice

Abstract

Abstract Epidemiological studies have reported associations between exposure to ambient particulate matter (PM) and neurocognitive impairments. Children are particularly vulnerable to the effects of PM since their CNS is still in development, especially in regions related to executive functions (EFs). Toxicological studies have reported oxidative stress and neuroinflammatory responses in mice exposed to different types of PM. However, most studies have focused on prenatal, perinatal, and adult PM exposures. The goal of this study was to assess if PM exposure impairs the postnatal development of EF. We hypothesized that exposure to diesel exhaust particles (DEP) will impair EFs by inducing inflammatory responses in the CNS and lungs. To test this hypothesis, female and male C57BL/6J mice (n=14/group) were exposed intranasally to either saline or increasing doses of DEP during postnatal days (PND) 25 to 33. General cognitive abilities and executive function were evaluated on PND 36–38 with the Puzzle Box paradigm. Mice were euthanized on PND 39 and the tissue was collected to measure the concentration of proinflammatory cytokines in the CNS and assess inflammatory cell influx into the lungs. In the brain, the levels of IL-6 and GM-CSF, but not TNFα, significantly increased in a dose-dependent manner. In the lungs, a dose-dependent influx of inflammatory cells was also observed. The results showed that mice exposed to DEP had concomitant deficits in cognitive processes related to executive functions and inflammatory responses in the brain and lungs. This suggest that DEP induced pro-inflammatory responses might be associated with deficitis in the postnatal development of EFs. In the future, the role of microglia activation will be explored. Supported by Puerto Rico IDeA Network of Biomedical Research Excellence 5P20GM103475-18.