請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69955
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林靖愉 | zh_TW |
dc.contributor.author | 李沛軒 | zh_TW |
dc.contributor.author | Pei-Hsuan Lee | en |
dc.date.accessioned | 2021-06-17T03:35:54Z | - |
dc.date.available | 2023-12-15 | - |
dc.date.copyright | 2018-03-29 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | 1. Pope CA, 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD: Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002, 287(9):1132-1141.
2. Lo WC, Shie RH, Chan CC, Lin HH: Burden of disease attributable to ambient fine particulate matter exposure in Taiwan. J Formos Med Assoc 2017, 116(1):32-40. 3. Wilker EH, Preis SR, Beiser AS, Wolf PA, Au R, Kloog I, Li W, Schwartz J, Koutrakis P, DeCarli C et al: Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure. Stroke 2015, 46(5):1161-1166. 4. Chen JC, Wang X, Wellenius GA, Serre ML, Driscoll I, Casanova R, McArdle JJ, Manson JE, Chui HC, Espeland MA: Ambient air pollution and neurotoxicity on brain structure: Evidence from women's health initiative memory study. Ann Neurol 2015, 78(3):466-476. 5. Kioumourtzoglou MA, Schwartz JD, Weisskopf MG, Melly SJ, Wang Y, Dominici F, Zanobetti A: Long-term PM2.5 Exposure and Neurological Hospital Admissions in the Northeastern United States. Environ Health Perspect 2016, 124(1):23-29. 6. Ailshire JA, Crimmins EM: Fine particulate matter air pollution and cognitive function among older US adults. Am J Epidemiol 2014, 180(4):359-366. 7. Lilian C-G, Anna CS, Carlos H-R, Ricardo T-J, Bryan N, Lou H, Rafael V-C, Norma O, Ida S, Raquel G et al: Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults. Toxicologic Pathology 2008, 36(2):289-310. 8. Block ML, Calderon-Garciduenas L: Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci 2009, 32(9):506-516. 9. Li XY, Hao L, Liu YH, Chen CY, Pai VJ, Kang JX: Protection against fine particle-induced pulmonary and systemic inflammation by omega-3 polyunsaturated fatty acids. Biochim Biophys Acta 2017, 1861(3):577-584. 10. Genc S, Zadeoglulari Z, Fuss SH, Genc K: The adverse effects of air pollution on the nervous system. J Toxicol 2012, 2012:782462. 11. Xing Y-F, Xu Y-H, Shi M-H, Lian Y-X: The impact of PM2.5 on the human respiratory system. Journal of Thoracic Disease 2016, 8(1):E69-E74. 12. Kelly F: Oxidative stress: its role in air pollution and adverse health effects. Occupational and Environmental Medicine 2003, 60(8):612-616. 13. Mehta M, Chen LC, Gordon T, Rom W, Tang MS: Particulate matter inhibits DNA repair and enhances mutagenesis. Mutation research 2008, 657(2):116-121. 14. Fagundes LS, Fleck Ada S, Zanchi AC, Saldiva PH, Rhoden CR: Direct contact with particulate matter increases oxidative stress in different brain structures. Inhal Toxicol 2015, 27(10):462-467. 15. Wu Y-L: CNS Toxicity Induced by DEPs and Ambient Particles. 2016. 16. Wu C, Chen ST, Peng KH, Cheng TJ, Wu KY: Concurrent quantification of multiple biomarkers indicative of oxidative stress status using liquid chromatography-tandem mass spectrometry. Anal Biochem 2016, 512:26-35. 17. Lobo V, Patil A, Phatak A, Chandra N: Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews 2010, 4(8):118-126. 18. Guerra R, Vera-Aguilar E, Uribe-Ramirez M, Gookin G, Camacho J, Osornio-Vargas AR, Mugica-Alvarez V, Angulo-Olais R, Campbell A, Froines J et al: Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum. Toxicol Lett 2013, 222(2):146-154. 19. Zanchi AC, Fagundes LS, Barbosa F, Jr., Bernardi R, Rhoden CR, Saldiva PH, do Valle AC: Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress. Inhal Toxicol 2010, 22(11):910-918. 20. Shah AS, Lee KK, McAllister DA, Hunter A, Nair H, Whiteley W, Langrish JP, Newby DE, Mills NL: Short term exposure to air pollution and stroke: systematic review and meta-analysis. BMJ 2015, 350:h1295. 21. Chen H, Kwong JC, Copes R, Hystad P, van Donkelaar A, Tu K, Brook JR, Goldberg MS, Martin RV, Murray BJ et al: Exposure to ambient air pollution and the incidence of dementia: A population-based cohort study. Environ Int 2017, 108:271-277. 22. Gasecki D, Kwarciany M, Nyka W, Narkiewicz K: Hypertension, brain damage and cognitive decline. Curr Hypertens Rep 2013, 15(6):547-558. 23. Bagate K, Meiring JJ, Gerlofs-Nijland ME, Vincent R, Cassee FR, Borm PJ: Vascular effects of ambient particulate matter instillation in spontaneous hypertensive rats. Toxicol Appl Pharmacol 2004, 197(1):29-39. 24. Ying Z, Xie X, Bai Y, Chen M, Wang X, Zhang X, Morishita M, Sun Q, Rajagopalan S: Exposure to concentrated ambient particulate matter induces reversible increase of heart weight in spontaneously hypertensive rats. Part Fibre Toxicol 2015, 12:15. 25. Chang C-C, Hwang J-S, Chan C-C, Wang P-Y, Hu T-H, Cheng T-J: Effects of Concentrated Ambient Particles on Heart Rate, Blood Pressure, and Cardiac Contractility in Spontaneously Hypertensive Rats. Inhalation Toxicology 2004, 16(6-7):421-429. 26. Akpaffiong MJ, Taylor AA: Antihypertensive and Vasodilator Actions of Antioxidants in Spontaneously Hypertensive Rats*. American Journal of Hypertension 1998, 11(12):1450-1460. 27. Li H, Cai J, Chen R, Zhao Z, Ying Z, Wang L, Chen J, Hao K, Kinney PL, Chen H et al: Particulate Matter Exposure and Stress Hormone Levels: A Randomized, Double-Blind, Crossover Trial of Air Purification. Circulation 2017, 136(7):618-627. 28. Wang X-F, Jiang S-F, Zhang W-B, Zhang L-Y, Liu Y, Du X-Y, Zhang J, Shen H-Q: Study on Reproductive Toxicity of Fine Particulate Matter by Metabolomics. Chinese Journal of Analytical Chemistry 2017, 45(5):633-640. 29. Zhang SY, Shao D, Liu H, Feng J, Feng B, Song X, Zhao Q, Chu M, Jiang C, Huang W et al: Metabolomics analysis reveals that benzo[a]pyrene, a component of PM2.5, promotes pulmonary injury by modifying lipid metabolism in a phospholipase A2-dependent manner in vivo and in vitro. Redox Biol 2017, 13:459-469. 30. Cheng KT: Metabolic Effects of Sub-chronic Ambient Particulate Matter Inhalation Exposure in Sprague-Dawley Rats. 2013. 31. Chen WL, Lin CY, Yan YH, Cheng KT, Cheng TJ: Alterations in rat pulmonary phosphatidylcholines after chronic exposure to ambient fine particulate matter. Mol Biosyst 2014, 10(12):3163-3169. 32. Han X: Neurolipidomics: challenges and developments. Front Biosci 2007, 12:2601-2615. 33. Adibhatla RM, Hatcher JF: Role of Lipids in Brain Injury and Diseases. Future Lipidol 2007, 2(4):403-422. 34. Kosicek M, Hecimovic S: Phospholipids and Alzheimer's disease: alterations, mechanisms and potential biomarkers. Int J Mol Sci 2013, 14(1):1310-1322. 35. Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH, Jr., Murphy RC, Raetz CR, Russell DW, Seyama Y, Shaw W et al: A comprehensive classification system for lipids. J Lipid Res 2005, 46(5):839-861. 36. Wenk MR: The emerging field of lipidomics. Nat Rev Drug Discov 2005, 4(7):594-610. 37. Hannun YA, Luberto C, Argraves KM: Enzymes of sphingolipid metabolism: from modular to integrative signaling. Biochemistry 2001, 40(16):4893-4903. 38. van Meer G: Cellular lipidomics. EMBO J 2005, 24(18):3159-3165. 39. Hyvönen MT, Kovanen PT: Molecular dynamics simulations of unsaturated lipid bilayers: effects of varying the numbers of double bonds. European Biophysics Journal 2005, 34(4):294-305. 40. Farooqui AA, Horrocks LA, Farooqui T: Glycerophospholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipids 2000, 106(1):1-29. 41. Barth C, Stark G: Radiation inactivation of ion channels formed by gramicidin A. Protection by lipid double bonds and by α-tocopherol. Biochimica et Biophysica Acta (BBA) - Biomembranes 1991, 1066(1):54-58. 42. Chen X, Gross RW: Phospholipid Subclass-Specific Alterations in the Kinetics of Ion-Transport across Biologic Membranes. Biochemistry 1994, 33(46):13769-13774. 43. Lindahl M, Bruhn R, Tagesson C: Lysophosphatidylcholine and the inflammatory action of neutrophils. Scandinavian Journal of Clinical and Laboratory Investigation 2009, 48(4):303-311. 44. Nishiyama O, Kume H, Kondo M, Ito Y, Ito M, Yamaki K: Role of lysophosphatidylcholine in eosinophil infiltration and resistance in airways. Clinical and experimental pharmacology & physiology 2004, 31(3):179-184. 45. Merrill AH, Jr., Sullards MC, Allegood JC, Kelly S, Wang E: Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 2005, 36(2):207-224. 46. Naudi A, Cabre R, Jove M, Ayala V, Gonzalo H, Portero-Otin M, Ferrer I, Pamplona R: Lipidomics of human brain aging and Alzheimer's disease pathology. Int Rev Neurobiol 2015, 122:133-189. 47. Cutler R: Sphingomyelin and ceramide as regulators of development and lifespan. Mechanisms of Ageing and Development 2001, 122(9):895-908. 48. Dressler K, Mathias S, Kolesnick R: Tumor necrosis factor-alpha activates the sphingomyelin signal transduction pathway in a cell-free system. Science 1992, 255(5052):1715-1718. 49. Brann AB, Tcherpakov M, Williams IM, Futerman AH, Fainzilber M: Nerve growth factor-induced p75-mediated death of cultured hippocampal neurons is age-dependent and transduced through ceramide generated by neutral sphingomyelinase. J Biol Chem 2002, 277(12):9812-9818. 50. Crivello NA, Rosenberg IH, Dallal GE, Bielinski D, Joseph JA: Age-related changes in neutral sphingomyelin-specific phospholipase C activity in striatum, hippocampus, and frontal cortex: implication for sensitivity to stress and inflammation. Neurochem Int 2005, 47(8):573-579. 51. Green DR: Apoptosis and Sphingomyelin Hydrolysis: The Flip Side. The Journal of Cell Biology 2000, 150(1):5-8. 52. Zhao L, Spassieva SD, Jucius TJ, Shultz LD, Shick HE, Macklin WB, Hannun YA, Obeid LM, Ackerman SL: A deficiency of ceramide biosynthesis causes cerebellar purkinje cell neurodegeneration and lipofuscin accumulation. PLoS Genet 2011, 7(5):e1002063. 53. Sato Y, Bernier F, Suzuki I, Kotani S, Nakagawa M, Oda Y: Comparative lipidomics of mouse brain exposed to enriched environment. J Lipid Res 2013, 54(10):2687-2696. 54. Chan RB, Oliveira TG, Cortes EP, Honig LS, Duff KE, Small SA, Wenk MR, Shui G, Di Paolo G: Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem 2012, 287(4):2678-2688. 55. Piomelli D: The challenge of brain lipidomics. Prostaglandins Other Lipid Mediat 2005, 77(1-4):23-34. 56. Zhang T, Chen S, Liang X, Zhang H: Development of a mass-spectrometry-based lipidomics platform for the profiling of phospholipids and sphingolipids in brain tissues. Anal Bioanal Chem 2015, 407(21):6543-6555. 57. Ivanisevic J, Epstein AA, Kurczy ME, Benton PH, Uritboonthai W, Fox HS, Boska MD, Gendelman HE, Siuzdak G: Brain region mapping using global metabolomics. Chem Biol 2014, 21(11):1575-1584. 58. Smith CA, Farmer K, Lee H, Holahan MR, Smith JC: Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Rats. Int J Environ Res Public Health 2015, 12(10):13542-13559. 59. Tang CH, Tsao PN, Chen CY, Shiao MS, Wang WH, Lin CY: Glycerophosphocholine molecular species profiling in the biological tissue using UPLC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2011, 879(22):2095-2106. 60. Yan YH, C CKC, Wang JS, Tung CL, Li YR, Lo K, Cheng TJ: Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model. Toxicol Appl Pharmacol 2014, 281(2):211-220. 61. Folch J, Ascoli I, Lees M, Meath JA, Le BN: Preparation of lipide extracts from brain tissue. J Biol Chem 1951, 191(2):833-841. 62. Tang CH, Tsao PN, Lin CY, Fang LS, Lee SH, Wang WH: Phosphorylcholine-containing lipid molecular species profiling in biological tissue using a fast HPLC/QqQ-MS method. Anal Bioanal Chem 2012, 404(10):2949-2961. 63. Pluskal T, Castillo S, Villar-Briones A, Oresic M: MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. Bmc Bioinformatics 2010, 11. 64. Vinaixa M, Samino S, Saez I, Duran J, Guinovart JJ, Yanes O: A Guideline to Univariate Statistical Analysis for LC/MS-Based Untargeted Metabolomics-Derived Data. Metabolites 2012, 2(4):775-795. 65. Worley B, Powers R: Multivariate Analysis in Metabolomics. Curr Metabolomics 2013, 1(1):92-107. 66. Chavko M, Nemoto E, A. Melick J: Regional lipid composition in the rat brain, vol. 18; 1993. 67. Yeagle PL: Biogenesis of Membrane Lipids. 2016. 68. Braverman NE, Moser AB: Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta 2012, 1822(9):1442-1452. 69. Lee T-c: Biosynthesis and possible biological functions of plasmalogens. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1998, 1394(2):129-145. 70. McIntyre TM, Snyder F, Marathe GK: CHAPTER 9 - Ether-linked lipids and their bioactive species A2 - Vance, Dennis E. In: Biochemistry of Lipids, Lipoproteins and Membranes (Fifth Edition). Edited by Vance JE. San Diego: Elsevier; 2008: 245-276. 71. Alfred H.Merrill CCS: Sphingolipids: metabolism and cell signalling. 1996. 72. Adibhatla RM, Hatcher JF, Dempsey RJ: Lipids and lipidomics in brain injury and diseases. AAPS J 2006, 8(2):E314-321. 73. Squire LR: Memory and brain systems: 1969-2009. J Neurosci 2009, 29(41):12711-12716. 74. Fonken LK, Xu X, Weil ZM, Chen G, Sun Q, Rajagopalan S, Nelson RJ: Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Mol Psychiatry 2011, 16(10):987-995, 973. 75. Chao MW, Yang CH, Lin PT, Yang YH, Chuang YC, Chung MC, Tseng CY: Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus. Environ Toxicol 2017, 32(4):1412-1425. 76. Bazinet RP, Laye S: Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 2014, 15(12):771-785. 77. Gorgas K, Teigler A, Komljenovic D, Just WW: The ether lipid-deficient mouse: tracking down plasmalogen functions. Biochim Biophys Acta 2006, 1763(12):1511-1526. 78. Panganamala RV, Horrocks LA, Geer JC, Cornwell DG: Positions of double bonds in the monounsaturated alk-1-enyl groups from the plasmalogens of human heart and brain. In: Chemistry and Physics of Lipids. vol. 6; 1971: 97-102. 79. Tang CH, Fang LS, Fan TY, Wang LH, Lin CY, Lee SH, Wang WH: Cellular membrane accommodation to thermal oscillations in the coral Seriatopora caliendrum. PLoS One 2014, 9(8):e105345. 80. Tepper AD, Ruurs P, Wiedmer T, Sims PJ, Borst J, van Blitterswijk WJ: Sphingomyelin Hydrolysis to Ceramide during the Execution Phase of Apoptosis Results from Phospholipid Scrambling and Alters Cell-Surface Morphology. The Journal of Cell Biology 2000, 150(1):155-164. 81. Liu JJ, Green P, John Mann J, Rapoport SI, Sublette ME: Pathways of polyunsaturated fatty acid utilization: implications for brain function in neuropsychiatric health and disease. Brain Res 2015, 1597:220-246. 82. Bazan NG: Lipid signaling in neural plasticity, brain repair, and neuroprotection. Molecular Neurobiology 2005, 32(1):89-103. 83. Wang ZJ, Liang CL, Li GM, Yu CY, Yin M: Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices. Chem Biol Interact 2006, 163(3):207-217. 84. Strokin M, Chechneva O, Reymann KG, Reiser G: Neuroprotection of rat hippocampal slices exposed to oxygen–glucose deprivation by enrichment with docosahexaenoic acid and by inhibition of hydrolysis of docosahexaenoic acid-containing phospholipids by calcium independent phospholipase A2. Neuroscience 2006, 140(2):547-553. 85. Megli FM, Russo L: Different oxidized phospholipid molecules unequally affect bilayer packing. Biochim Biophys Acta 2008, 1778(1):143-152. 86. Akhlaq A. Farooqui TF, Lloyd A. Horrocks: Metabolism and Functions of Bioactive Ether Lipids in the Brain; 2008. 87. Hannun YA, Obeid LM: Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 2008, 9(2):139-150. 88. Posse de Chaves E, Sipione S: Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. FEBS Lett 2010, 584(9):1748-1759. 89. Oenzil F, Kishikawa M, Mizuno T, Nakano M: Age-related accumulation of lipofuscin in three different regions of rat brain. Mech Ageing Dev 1994, 76(2-3):157-163. 90. Cho S, Hwang ES: Chapter 7 - Fluorescence-Based Detection and Quantification of Features of Cellular Senescence. In: Methods in Cell Biology. Edited by Darzynkiewicz Z, Holden E, Orfao A, Telford W, Wlodkowic D, vol. 103: Academic Press; 2011: 149-188. 91. Jung T, Bader N, Grune T: Lipofuscin. Annals of the New York Academy of Sciences 2007, 1119(1):97-111. 92. D’Andrea MR: Chapter 4 - Addressing Technical Concerns. In: Bursting Neurons and Fading Memories. San Diego: Academic Press; 2015: 33-41. 93. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C: Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 2004, 16(6-7):437-445. 94. Paine MG, Che D, Li L, Neumar RW: Cerebellar Purkinje cell neurodegeneration after cardiac arrest: effect of therapeutic hypothermia. Resuscitation 2012, 83(12):1511-1516. 95. Smith HL, Howland MC, Szmodis AW, Li Q, Daemen LL, Parikh AN, Majewski J: Early stages of oxidative stress-induced membrane permeabilization: a neutron reflectometry study. J Am Chem Soc 2009, 131(10):3631-3638. 96. Wolf BB, Green DR: Suicidal Tendencies: Apoptotic Cell Death by Caspase Family Proteinases. Journal of Biological Chemistry 1999, 274(29):20049-20052. 97. Wang W, Deng Z, Feng Y, Liao F, Zhou F, Feng S, Wang X: PM2.5 induced apoptosis in endothelial cell through the activation of the p53-bax-caspase pathway. Chemosphere 2017, 177:135-143. 98. Yin J, Xia W, Li Y, Guo C, Zhang Y, Huang S, Jia Z, Zhang A: COX-2 mediates PM2.5-induced apoptosis and inflammation in vascular endothelial cells. American Journal of Translational Research 2017, 9(9):3967-3976. 99. Hall SM: The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci 1972, 10(2):535-546. 100. Kostrzewa RM, Segura-Aguilar J: Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. a review. Neurotoxicity research 2003, 5(6):375-383. 101. Jean I, Allamargot C, Barthelaix-Pouplard A, Fressinaud C: Axonal lesions and PDGF-enhanced remyelination in the rat corpus callosum after lysolecithin demyelination. Neuroreport 2002, 13(5):627-631. 102. Choi J, Yin T, Shinozaki K, Lampe JW, Stevens JF, Becker LB, Kim J: Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids. Mol Cell Biochem 2017. 103. Chakravarthy MV, Lodhi IJ, Yin L, Malapaka RRV, Xu HE, Turk J, Semenkovich CF: Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver. Cell 2009, 138(3):476-488. 104. Zheng Z, Zhang X, Wang J, Dandekar A, Kim H, Qiu Y, Xu X, Cui Y, Wang A, Chen LC et al: Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. J Hepatol 2015, 63(6):1397-1404. 105. Solleti SK, Simon DM, Srisuma S, Arikan MC, Bhattacharya S, Rangasamy T, Bijli KM, Rahman A, Crossno JT, Shapiro SD et al: Airway epithelial cell PPARγ modulates cigarette smoke-induced chemokine expression and emphysema susceptibility in mice. American Journal of Physiology - Lung Cellular and Molecular Physiology 2015, 309(3):L293-L304. 106. Zheng Z, Xu X, Zhang X, Wang A, Zhang C, Huttemann M, Grossman LI, Chen LC, Rajagopalan S, Sun Q et al: Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. J Hepatol 2013, 58(1):148-154. 107. Heneka MT, Landreth GE: PPARs in the brain. Biochim Biophys Acta 2007, 1771(8):1031-1045. 108. Moreno S, Farioli-Vecchioli S, Cerù MP: Immunolocalization of peroxisome proliferator-activated receptors and retinoid x receptors in the adult rat CNS. Neuroscience 2004, 123(1):131-145. 109. Cullingford TE, Bhakoo K, Peuchen S, Dolphin CT, Patel R, Clark JB: Distribution of mRNAs Encoding the Peroxisome Proliferator-Activated Receptor α, β, and γ and the Retinoid X Receptor α, β, and γ in Rat Central Nervous System. Journal of Neurochemistry 2002, 70(4):1366-1375. 110. Cheng M, Pan H, Dai Y, Zhang J, Tong Y, Huang Y, Wang M, Huang H: Phosphatidylcholine regulates NF-κB activation in attenuation of LPS-induced inflammation: evidence from in vitro study. Animal Cells and Systems 2017:1-8. 111. Wang HY, Liu CB, Wu HW, Kuo JS: Direct profiling of phospholipids and lysophospholipids in rat brain sections after ischemic stroke. Rapid Commun Mass Spectrom 2010, 24(14):2057-2064. 112. Rao Muralikrishna Adibhatla JFH, Eric C. Larsen,Xinzhi Chen, Dandan Sun, and Francis H. C. Tsao: CDP-choline significantly restores phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP: phosphocholine cytidylyltransferase after stroke. J Biol Chem 2013, 288(11):7549. 113. Liu X-F, Fawcett JR, Thorne RG, DeFor TA, Frey WH: Intranasal administration of insulin-like growth factor-I bypasses the blood–brain barrier and protects against focal cerebral ischemic damage. Journal of the Neurological Sciences 2001, 187(1-2):91-97. 114. Calderón-Garcidueña L, Maronpot RR, Torres-Jardon R, Henríquez-Roldán C, Schoonhoven R, Acuña-Ayala H, Villarreal-Calderón A, Nakamura J, Fernando R, Reed W et al: DNA Damage in Nasal and Brain Tissues of Canines Exposed to Air Pollutants Is Associated with Evidence of Chronic Brain Inflammation and Neurodegeneration. Toxicologic Pathology 2003, 31(5):524-538. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69955 | - |
dc.description.abstract | 空氣汙染所造成的健康危害日趨嚴重,過去的流行病學研究和動物研究皆已經證實大氣細懸浮微粒(PM2.5)與呼吸系統和心血管系統的不良健康效應有關。而近幾年流行病學研究發現長期暴露大氣細懸浮微粒可能造成中樞神經系統的不良影響,如認知功能下降、大腦結構改變以及加速大腦老化速度,甚至與神經退化性疾病有關。由於大腦為脂質含量非常豐富之器官,我們假設暴露大氣懸浮微離會造成腦脂質組成改變,此改變可能造成大腦功能障礙或腦部傷害。我們希望利用質譜儀為基礎的脂質體學,針對大腦中重要的脂質-磷脂醯膽鹼(Phosphatidylcholines)和神經磷脂(Sphingomyelins),以探討亞慢性暴露大氣細懸浮微粒對大腦所造成的影響,進一步釐清可能的毒理機制。
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。 PLS-DA結果顯示五個腦區的脂質體在暴露組和控制組之間皆呈現分群,其中,PM2.5對海馬迴的脂質造成最大影響,且顯著改變的脂質體在海馬迴及小腦有相同的變化趨勢。在海馬迴中多元不飽和diacyl-phosphatidylcholines、plasmanylcholines以及plasmenylcholines皆有顯著上升的趨勢,而有些sphingomyelins在海馬迴及小腦中也呈現顯著上升,透過代謝途徑的推測,這些脂質可能在海馬迴及小腦中扮演著神經保護性機制,以防禦PM2.5可能導致之氧化壓力及細胞損傷;在大腦髓質中發現部份diacyl-phosphatidylcholines顯著下降且lyso-phosphatidylcholines顯著上升,另外在大腦皮質中少數的飽和plasmanylcholines、飽和plasmenylcholines及sphingomyelins呈現顯著下降,此結果顯示PM2.5暴露可能造成大腦皮質和大腦髓質中的脂質產生擾動,導致細胞膜不穩定、發炎反應、及抗氧化能力下降;而在嗅球則未發現顯著的脂質改變。我們利用脂質體學的方法觀察到海馬迴及小腦的脂質體改變趨勢與其他腦區有差異。然而總顯著改變的脂質不多,我們推測可能與低濃度及亞慢性暴露有關。 本研究證實亞慢性暴露大氣PM2.5會造成自發性高血壓大鼠的海馬迴、小腦、大腦皮質、大腦髓質以及嗅球之phosphatidylcholines和sphingomyelins產生擾動,在不同腦區觀察到脂質有不同的改變趨勢,可能與特定腦區對PM2.5的易感受性和傷害不同有關。此外,本研究可支持以質譜為基礎的脂質體學為一個有效的方法以探討暴露與可能之健康效應的相關性,並幫助建議未來在公共衛生研究上的方向。 | zh_TW |
dc.description.abstract | 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. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T03:35:54Z (GMT). No. of bitstreams: 1 ntu-107-R04844014-1.pdf: 1953332 bytes, checksum: f5c49f9f904a98cebb254e51ad525f31 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 致謝 ................................................................................................................................... i
摘要 .................................................................................................................................. ii Abstract............................................................................................................................ iv Content ............................................................................................................................ vi List of Tables................................................................................................................. viii List of Figures.................................................................................................................. ix Chapter 1. Introduction..................................................................................................... 1 1.1 Background............................................................................................................. 1 1.2 Particulate matter and metabolic alteration............................................................. 3 1.3 Brain lipidomics...................................................................................................... 4 1.4 Study aim ................................................................................................................ 7 Chapter 2. Material and methods...................................................................................... 8 2.1 Experimental flow chart.......................................................................................... 8 2.2 Animal study design ............................................................................................... 9 2.2.1 Animal handling............................................................................................... 9 2.2.2 Exposure system............................................................................................... 9 2.3 Sampling and analysis of phosphorylcholine-containing lipids ........................... 10 2.3.1 Brain tissue collection and pretreatment ........................................................ 10 2.3.2 Acquisition of brain lipidome ........................................................................ 11 2.3.3 Identification of phosphorylcholine-containing lipids ................................... 12 2.4 Chemometrics ....................................................................................................... 13 2.4.1 Spectral preprocessing.................................................................................... 13 2.4.2 Handling analytical variation ......................................................................... 14 2.4.3 Multivariate analysis ...................................................................................... 14 2.4.4 Univariate analysis ......................................................................................... 16 Chapter 3. Results........................................................................................................... 17 3.1 Summary of animals after ambient PM2.5 exposure ............................................. 17 3.2 PM levels and chemical composition ................................................................... 17 3.3 Phosphorylcholine-containing lipid profiling in the brain.................................... 17 3.4 Effects of ambient PM2.5 on phosphorylcholine–containing lipids in different brain regions ............................................................................................................... 19 3.4.1 Hippocampus.................................................................................................. 20 3.4.2 Cerebellum ..................................................................................................... 20 3.4.3 Cerebral cortex ............................................................................................... 21 3.4.4 Cerebral medulla ............................................................................................ 22 3.4.5 Olfactory bulb ................................................................................................ 23 Chapter 4. Discussion..................................................................................................... 24 4.1 The compositions of lipids in different brain regions........................................... 24 4.2 Effects of ambient PM2.5 matter on lipidome of different brain regions .............. 25 4.2.1 Hippocampus.................................................................................................. 26 4.2.1.1 The changed phosphorylcholine-containing lipids may promote integrity on cell membrane................................................................................................ 27 4.2.1.2 The increased polyunsaturated diacyl-phosphatidylcholines may affect cell development processes ................................................................................ 28 4.2.1.3 The increased plasmenylcholines may act as anti-oxidant..................... 29 4.2.1.4 The increased sphingomyelins may protect against ambient PM2.5-induced lipofuscin accumulation........................................................................ 29 4.2.2 Cerebellum..................................................................................................... 30 4.2.3 Cerebral cortex ............................................................................................... 31 4.2.4 Cerebral medulla ............................................................................................ 32 4.2.5 Olfactory bulb ................................................................................................ 33 4.3 Strengths, limitations and future work.................................................................. 33 Chapter 5. Conclusion .................................................................................................... 35 Reference ........................................................................................................................ 36 Appendix ........................................................................................................................ 69 | - |
dc.language.iso | zh_TW | - |
dc.title | 利用自發性高血壓大鼠探討亞慢性呼吸暴露大氣細懸浮微粒對大腦脂質的影響 | zh_TW |
dc.title | Effect of Sub-chronic Exposure to Ambient Fine Particulate Matter on the Brain Lipids of Spontaneously Hypertensive Rat | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-1 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 鄭尊仁;唐川禾 | zh_TW |
dc.contributor.oralexamcommittee | ;; | en |
dc.subject.keyword | 懸浮微粒,質譜儀,大腦,海馬迴,脂質體學,磷脂醯膽鹼,神經磷脂, | zh_TW |
dc.subject.keyword | Particulate matter,Mass spectrometry,Brain,Hippocampus,Lipidomics,Phosphatidylcholine,Sphingomyelin, | en |
dc.relation.page | 87 | - |
dc.identifier.doi | 10.6342/NTU201800553 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-02-12 | - |
dc.contributor.author-college | 公共衛生學院 | - |
dc.contributor.author-dept | 環境衛生研究所 | - |
顯示於系所單位: | 環境衛生研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-1.pdf 目前未授權公開取用 | 1.91 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。