Brain lipid profiles in the spontaneously hypertensive rat after subchronic real-world exposure to ambient fine particulate matter

Abstract Recent studies have illustrated an association between ambient fine particulate matter (PM2.5) exposure and neuronal toxicity in epidemiological studies and animal models. However, the possible molecular effects on brains under real-world exposure to PM2.5 remain unclear. In this pilot study, male spontaneously hypertensive rats were whole-bodily exposed to ambient air from the outdoor environment of Taipei City for 3 months, while the control rats inhaled HEPA-filtered air. The PM2.5-induced phosphatidylcholine and sphingomyelin profiles in the hippocampus, cortex, medulla, cerebellum, and olfactory bulb were assessed by mass spectrometry (MS)-based lipidomics. Partial least squares discriminant analysis (PLS-DA) and the Wilcoxon rank sum test were used to examine the lipid changes between the exposed and control groups. The PLS-DA models showed that phosphatidylcholine and sphingomyelin profiles of the PM2.5 exposure group were different from those of the control group in each brain region except the cortex. More lipid changes were found in the hippocampus, while fewer lipid changes were observed in the olfactory bulb. The lipid alteration in the hippocampus may strengthen membrane integrity, modulate signaling pathways, and avoid accumulation of lipofuscin to counter the PM2.5-induced stress. The lipid changes in the cortex and medulla may respond to PM2.5-induced injury and inflammation; while the lipid changes in the cerebellum were associated with neuron protection. This study suggests that the MS-based lipidomics is a powerful approach to discriminate the brain lipid profiles even at the environmental level of ambient PM2.5 and has the potential to suggest possible adverse health effects in long-term PM2.5 exposure studies.