An integrative analysis of lipidomics and transcriptomics in various mouse brain regions in response to real-ambient...

Exposure to Fine particulate matter (PM_2.5) has been associated with various neurological disorders. However, the underlying mechanisms of PM_2.5-induced adverse effects on the brain are still not fully defined. Multi-omics analyses could offer novel insights into the mechanisms of PM_2.5-induced brain dysfunction. In this study, a real-ambient PM_2.5 exposure system was applied to male C57BL/6 mice for 16 weeks, and lipidomics and transcriptomics analysis were performed in four brain regions. The findings revealed that PM_2.5 exposure led to 548, 283, 304, and 174 differentially expressed genes (DEGs), as well as 184, 89, 228, and 49 distinctive lipids in the hippocampus, striatum, cerebellum, and olfactory bulb, respectively. Additionally, in most brain regions, PM_2.5-induced DEGs were mainly involved in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, and calcium signaling pathway, while PM_2.5-altered lipidomic profile were primarily enriched in retrograde endocannabinoid signaling and biosynthesis of unsaturated fatty acids. Importantly, mRNA-lipid correlation networks revealed that PM_2.5-altered lipids and DEGs were obviously enriched in pathways involving in bile acid biosynthesis, De novo fatty acid biosynthesis, and saturated fatty acids beta-oxidation in brain regions. Furthermore, multi-omics analyses revealed that the hippocampus was the most sensitive part to PM_2.5 exposure. Specifically, dysregulation of Pla2g1b, Pla2g, Alox12, Alox15, and Gpx4 induced by PM_2.5 were closely correlated to the disruption of alpha-linolenic acid, arachidonic acid and linoleic acid metabolism in the hippocampus. In summary, our findings highlight differential lipidomic and transcriptional signatures of various brain regions by real-ambient PM_2.5 exposure, which will advance our understanding of potential mechanisms of PM_2.5-induecd neurotoxicity.