Neurodegenerative pathways and metabolic changes in the hippocampus and cortex of mice exposed to urban particulate matter: Insights from an integrated interactome analysis.

ABSTRACT

Recently, urban particulate matter (UPM) exposure has been associated with the development of brain disorders. This study uses bioinformatic analyses to elucidate the molecular unexplored mechanisms underlying the effects of UPM exposure on the brain. Mice are exposed to UPM (from 3 days to 20 weeks), and their behavioral patterns measured. We measure pathology and gene expression in the hippocampus and cortical regions of the brain. An integrated interactome of genes is established, which enriches information on metabolic processes. Using this network, we isolate the core genes that are differentially expressed in the samples. We observe cognitive loss and pathological changes in the brains of mice at 16 or 20 weeks of exposure. Through network analysis of core-differential genes and measurement of pathway activity, we identify differences in the response to UPM exposure between the hippocampus and cortex. However, neurodegenerative disease pathways are implicated in both tissues following short-term exposure to UPM. There were also significant changes in metabolic function in both tissues depending on UPM exposure time. Additionally, the cortex of UPM-exposed mice shows more similarities with psychiatric disorders than with neurodegenerative diseases. The connectivity map database is used to isolate genes contributing to changes in expression due to UPM exposure. New approaches for inhibiting or preventing the brain damage caused by UPM exposure can be developed by targeting the functions and selected genes identified in this study.