Nicole A. Pagán, Génesis D. Rivera, Amanda Mojica, Héctor J. Rosa, Karla M. Casillas, Loyda B. Méndez

Division of Science & Technology, Universidad Ana G. Méndez -Recinto de Carolina, Puerto Rico

Epidemiological studies have reported associations between air pollution exposure and impairments in children cognition. Executive functions are neurocognitive processes that require control and direction, such as goal-oriented behavior, planning, reasoning, problem solving, cognitive flexibility and self-regulation among others. Previous results from our laboratory, showed significant deficits in cognitive processes of problem-solving skills and shot-term memory tasks on mice exposed to diesel exhaust particles (DEP), but not in long-term memory, when compare to controls. Therefore, the results suggested that the cognitive effects were specific to executive functions. Studies have associated the adverse health effect of air pollutants to inflammatory responses. These responses have been linked to several Central Nervous System (CNS) disorders. In-vitro and in-vivo studies have showed an increase of proinflammatory markers in animal models after exposure to DEP in both lung and brain. These proinflammatory markers can be present on tissue or in circulation. Therefore, we hypothesized that cognitive deficits in DEP exposed mice is associated with concomitant inflammatory responses in the lung and brain.

To test this hypothesis, we measured the concentration of pro-inflammatory cytokines in brain tissue and assess the infiltration of inflammatory cell into the lungs. Briefly, C57BL/6J mice were exposed via intranasal instillation in postnatal days (PND) 25 to 33, to either saline or different concentrations of DEP (2.5 and 5 μg). After completing the cognitive and behavioral evaluations, mice were euthanized and bronchoalveolar lavage fluid (BALF) and tissue were collected for further processing. To evaluate pro-inflammatory responses in the CNS, the brain tissue was homogenized with PBS and a multiplex bead-based immunoassay was used to measure the concentration of cytokines. To assess the influx of inflammatory cell into the lungs, the number of macrophages, lymphocytes and granulocytes were quantified in the BALF after differential cytological staining. In the brain, analysis showed a significant dose-response increase in the concentration of IL-6 & GM-CSF in mice exposed to DEP, with a r2 ≥0.96, but not in TNF-a. GM-CSF was significantly increased at both DEP exposure doses but IL-6 only at the highest dose. In the lungs, DEP exposed mice showed a dose-dependent increase in the influx of inflammatory cells when compared to controls, with a r2 ≥ 0.9. This increase was significant in the number of granulocytes in the highest dose of DEP. Results suggest that the pro-inflammatory responses induced by DEP exposure might contributed to the cognitive deficits observed in mice.

Acknowledgement: This work was supported by Puerto Rico IDeA Network of Biomedical Research

Excellence 5P20GM103475-18.

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