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Effect of Sub-chronic Exposure to Ambient Fine Particulate Matter on the Brain Lipids of Spontaneously Hypertensive Rat
Particulate matter,Mass spectrometry,Brain,Hippocampus,Lipidomics,Phosphatidylcholine,Sphingomyelin,
|Publication Year :||2018|
本實驗利用將八週齡自發性高血壓(spontaneously hypertensive rat)公鼠，隨機分為暴露組及控制組各五隻，其中暴露組全身暴露於大氣微粒暴露系統，控制組暴露經HEPA過濾懸浮微粒之空氣。暴露時間為期三個月，犧牲後取下右腦並分為五個腦區：嗅球、小腦、大腦髓質、海馬迴以及大腦皮質，進行樣本前處理和脂質萃取後，再利用極致液相層析儀搭配串聯式質譜儀(UPLC-MS/MS)進行脂質體分析。經數據前處理後，利用多變量分析－偏最小平方判別分析(PLS-DA)觀察兩個組別的脂質體是否有分群的結果。另外，利用無母數單變量分析－Wilcoxon rank sum test找出兩組間顯著差異的phosphatidylcholines和sphingomyelins。
A large number of experimental and epidemiological studies have demonstrated the association between ambient fine particulate matter (PM2.5) with adverse effects of pulmonary and cardiovascular systems. However, recent epidemiological studies indi-cated that long term PM2.5 exposure could cause brain damage, such as cognitive de-cline, cerebral structure change and brain aging acceleration, and also associated with the risk of neurodegenerative diseases. Due to the brain is rich in lipids, we hypothe-size that PM2.5 may cause lipid alteration in brain, which may lead to brain dysfunction. We intend to identify possible critical lipids associated with PM2.5 exposure by MS-based lipidomic approach and further associate those changes with biological function.
In this study, five male spontaneously hypertensive rats were whole-body exposed to ambient air from outside of the building for 3 months, while the control (n=5) in-haled HEPA filtered air. After animals were sacrificed, five brain regions including ol-factory bulb, cerebellum, cerebral medulla, hippocampus and cerebral cortex were taken. Phosphorylcholine-containing lipids including phosphatidylcholines and sphin-gomyelins were extracted from each brain region, and profiled by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). MS spectra from the analysis of lipids from exposure and control animals were analyzed by partial least squares discriminant analysis (PLS-DA). Moreover, Wilcoxon rank sum tests were used to examine the significant changes between the two groups.
The results showed that the phosphorylcholine-containing lipid profiles of the ex-posure group were different from those of the control group in the PLS-DA models of each brain regions. The greatest lipid changes are in hippocampus. Moreover, the pat-tern of lipid changes in the hippocampus and cerebellum were similar. In the hippo-campus, increased polyunsaturated diacyl-phosphatidylcholines, plasmanylcholines, plasmenylcholines and sphingomyelins may play roles to strengthen membrane integ-rity and protect against PM2.5-induced oxidative stress. The increase of sphingomyelins in the hippocampus and cerebellum may attempt to protect against PM2.5-induced neu-ron death and degeneration. The hippocampus and cerebellum were likely to have neuroprotective effects. On the other hand, decrease of some di-acyl-phosphatidylcholines as well as increase of some lyso-phosphatidylcholines in the cerebral medulla, and decrease of saturated ether-linked phosphatidylcholines and sphingomyelins in the cerebral cortex indicated that membrane lipid perturbation may disrupt membrane raft integrity, regulate inflammatory responses, and decrease defense under PM2.5-induced stress. There were no significant changes of lipids in the olfactory bulb. Our result also indicated that PM2.5-induced lipid alteration was region-specific. However, although lipids are abundant in the brain, the numbers of changed lipids are few after ambient PM2.5 exposure. We suggested it may be due to low concentration and sub-chronic exposure.
In conclusion, our results demonstrated that sub-chronic exposure to relatively low levels of PM2.5 lead to the alteration of lipids in the brain tissue. Moreover, the changes of lipids in different brain regions may be associated with the susceptibility and impairment of brain regions to PM2.5. This study supported that MS-based lip-idomic approach is a powerful platform to examine the brain lipid perturbation by am-bient PM2.5, and also able to link the changes with possible adverse effects and provide information for further study.
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