| Summary: | 碩士 === 國立臺灣大學 === 職業醫學與工業衛生研究所 === 105 === Research has shown that particulate matter (PM) would have adverse effects on respiratory, cardiovascular and central nervous system (CNS) in vivo. Many studies have shown that PM would induce inflammation effects and oxidative stress in CNS. Recently, macroautophagy (simply called “autophagy” hereafter) has been a popular issue associated with neurodegenerative disease. Impairment of autophagy may lead to accumulation of misfolding proteins and cause Alzheimer’s disease or Parkinson’s disease. However, the effects of autophagy after exposure to PM through respiratory tract are not clear.
In our previous study, C57BL/6 mice were exposed to diesel exhaust particles (DEPs) by intratracheal instillation (ITI) and the animals were sacrificed at 24 hours after the exposure. We found that pro-inflammatory cytokines increased significantly in the brain. In this study, C57BL/6 mice were exposed to diesel exhaust particles (DEPs, total dose: 300 µg/mice) by ITI. Animals were euthanized at four different time points (6 h, 1 day, 3 days, 7 days) after the last exposure. Cerebellum, hippocampus and cerebral cortex were used to measure deoxyribonucleic acid (DNA) damage marker of reactive oxygen species (ROS), 8-hydroxy-2''-deoxyguanosine (8-OHdG), and DNA damage marker of reactive nitrogen species (RNS), 8-nitroguanine (8-NO2Gua). Besides, we also measured two markers of autophagy, beclin-1 and microtubule-associated protein 1 light chain 3 (LC3). In this study, we wanted to explore more about CNS toxicity induced by PM.
Our results showed that the concentration of 8-OHdG and 8-NO2Gua in exposure groups didn’t have any differences compared to control groups at four time points (Wilcoxon rank sum test). The outcomes of autophagy expression showed that LC3, the biomarker of later stage of autophagy, decreased in cerebral cortex at the third post-exposure day (p<0.05, Wilcoxon rank sum test) and beclin-1 didn’t have significant differences between control and exposure groups in three brain regions at four different time points. The histopathology of lung indicated that there were inflammation effects in exposure groups.
Scientists have found that inhibition of LC3 may be associated with RNS and may cause accumulation of damaged organelles as well as proteins. Therefore, our results may be associated with inflammation in brain. However, the RNS levels didn''t have significant differences between control groups and exposure groups in our study. Further study should explore more about the influences of autophagy by DEPs in detail.
In conclusion, acute exposure of DEPs would impair autophagy in cerebral cortex. Our study revealed the possible mechanism of PM exposure and CNS diseases. Further study should explore the mechanism of how PM impact autophagy and the relationship between ROS/RNS and autophagy.
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