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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 賴向華(Hsiang-Hua Lai) | |
dc.contributor.author | Chia-Chun Tu | en |
dc.contributor.author | 杜佳駿 | zh_TW |
dc.date.accessioned | 2021-06-17T09:11:55Z | - |
dc.date.issued | 2020 | |
dc.date.submitted | 2021-03-24 | |
dc.identifier.citation | Aijie, C., Huimin, L., Jia, L., Lingling, O., Limin, W., Junrong, W., Xuan, L., Xue, H., Longquan, S., 2017. Central neurotoxicity induced by the instillation of ZnO and TiO2 nanoparticles through the taste nerve pathway. Nanomedicine (Lond) 12, 2453-2470. Ali, S., Rajini, P., 2012. Elicitation of dopaminergic features of Parkinson's disease in C. elegans by monocrotophos, an organophosphorous insecticide. CNS Neurol Disord Drug Targets 11, 993-1000. An, J., Blackwell, T., 2003. SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17, 1882-1893. Blackwell, T., Steinbaugh, M., Hourihan, J., Ewald, C., Isik, M., 2015. SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med 88, 290-301. Bonifati, V., Rizzu, P., van Baren, M., Schaap, O., Breedveld, G., Krieger, E., Dekker, M., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J., Vanacore, N., van Swieten, J., Brice, A., Meco, G., van Duijn, C., Oostra, B., Heutink, P., 2003. Mutations in the dj-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256-259. Braak, H., Del Tredici, K., 2008. Invited article: nervous system pathology in sporadic Parkinson disease. Neurology 70, 1916-1925. Cao, B., Wang, Y., Li, N., Liu, B., Zhang, Y., 2013. Preparation of an orthodontic bracket coated with an nitrogen-doped TiO(2-x)N(y) thin film and examination of its antimicrobial performance. Dent Mater J 32, 311-316. Carmo, T., Siqueira, P., Azevedo, V., Tavares, D., Pesenti, E., Cestari, M., Martinez, C., Fernandes, M., 2019. Overview of the toxic effects of titanium dioxide nanoparticles in blood, liver, muscles, and brain of a Neotropical detritivorous fish. Environ Toxicol 34, 457-468. Cooper, J., Van Raamsdonk, J., 2018. Modeling Parkinson's disease in C. elegans. J Parkinsons Dis 8, 17-32. Deng, J., Dai, Y., Tang, H., Pang, S., 2020. SKN-1 Is a Negative Regulator of DAF-16 and Somatic Stress Resistance in Caenorhabditis elegans. G3 (Bethesda) 10, 1707-1712. Esfandiari, N., Simchi, A., Bagheri, R., 2014. Size tuning of Ag-decorated TiO2 nanotube arrays for improved bactericidal capacity of orthopedic implants. J Biomed Mater Res A 102, 2625-2635. Esteban Florez, F., Hiers, R., Larson, P., Johnson, M., O'Rear, E., Rondinone, A., Khajotia, S., 2018. Antibacterial dental adhesive resins containing nitrogen-doped titanium dioxide nanoparticles. Mater Sci Eng C Mater Biol Appl 93, 931-943. Fahn, S., Cohen, G., 1992. The oxldant stress hypothesis in parkmson’s disease: evidence supporting it. Ann Neurol 32, 804-812. Fortin, D., Troyer, M., Nakamura, K., Kubo, S., Anthony, M., Edwards, R., 2004. Lipid rafts mediate the synaptic localization of alpha-synuclein. J Neurosci 24, 6715-6723. Hoogewijs, D., Houthoofd, K., Matthijssens, F., Vandesompele, J., Vanfleteren, J., 2008. Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans. BMC Mol Biol 9, 9. Hou, J., Wang, L., Wang, C., Zhang, S., Liu, H., Li, S., Wang, X., 2019. Toxicity and mechanisms of action of titanium dioxide nanoparticles in living organisms. J Environ Sci (China) 75, 40-53. Hu, Q., Guo, F., Zhao, F., Fu, Z., 2017. Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12. Chemosphere 173, 373-379. Ibrahim, M., Schoelermann, J., Mustafa, K., Cimpan, M., 2018. TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner. J Biomed Mater Res Part A 106, 2582-2593. Kalia, L., Lang, A., 2015. Parkinson's disease. Lancet 386, 896-912. Kirk, R., Othmer, D., Kroschwitz, J., Howe-Grant, M., 1991. Encyclopedia of chemical technologygy. 4th ed. New York. 397. Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., Shimizu, N., 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608. Klein, C., Westenberger, A., 2012. Genetics of Parkinson's disease. Cold Spring Harb Perspect Med 2, a008888. Kobayashi, M., Li, L., Iwamoto, N., Nakajima-Takagi, Y., Kaneko, H., Nakayama, Y., Eguchi, M., Wada, Y., Kumagai, Y., Yamamoto, M., 2009. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol Cell Biol 29, 493-502. Koziara, J., Lockman, P., Allen, D., Mumper, R., 2003. In situ blood-brain barrier transport of nanoparticles. Pharm Res 20, 1772-1778. Lan, A., Chen, J., Chai, Z., Hu, Y., 2016. The neurotoxicity of iron, copper and cobalt in Parkinson's disease through ROS-mediated mechanisms. Biometals 29, 665-678. Lee, J., Shih, A., Murphy, T., Johnson, J., 2003. NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem 278, 37948-37956. Li, W., Chang, C., Huang, C., Wei, C., Liao, V., 2014. Selenite enhances immune response against Pseudomonas aeruginosa PA14 via SKN-1 in Caenorhabditis elegans. PLoS One 9, e105810. Liao, V., 2018. Use of Caenorhabditis elegans to study the potential bioactivity of natural compounds. J Agric Food Chem 66, 1737-1742. Lin, J., Ren, W., Li, A., Yao, C., Chen, T., Ma, X., Wang, X., Wu, A., 2020. Crystal-Amorphous Core-Shell Structure Synergistically Enabling TiO2 Nanoparticles' Remarkable SERS Sensitivity for Cancer Cell Imaging. ACS Appl Mater Interfaces 12, 4204-4211. Liu, Z., Zhang, M., Han, X., Xu, H., Zhang, B., Yu, Q., Li, M., 2016. TiO2 nanoparticles cause cell damage independent of apoptosis and autophagy by impairing the ROS-scavenging system in Pichia pastoris. Chem Biol Interact 252, 9-18. Mak, S., McCormack, A., Manning-Bog, A., Cuervo, A., Di Monte, D., 2010. Lysosomal degradation of alpha-synuclein in vivo. J Biol Chem 285, 13621-13629. Manke, A., Wang, L., Rojanasakul, Y., 2013. Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed Res Int 2013, 942916. Meister, A., Anderson, M., 1983. Glutathione. Annu Rev Biochem 52, 711-760. Nass, R., Merchant, K., Ryan, T., 2008. Caenohabditis elegans in Parkinson's disease drug discovery: addressing an unmet medical need. Mol Interv 8, 283-293. Oberdorster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W., Cox, C., 2004. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16, 437-445. Oliveira, R., Porter Abate, J., Dilks, K., Landis, J., Ashraf, J., Murphy, C., Blackwell, T., 2009. Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell 8, 524-541. Parihar, M., Parihar, A., Fujita, M., Hashimoto, M., Ghafourifar, P., 2008. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci 65, 1272-1284. Pohl, F., Teixeira-Castro, A., Costa, M., Lindsay, V., Fiúza-Fernandes, J., Goua, M., Bermano, G., Russell, W., Maciel, P., Kong Thoo Lin, P., 2019. GST-4-dependent suppression of neurodegeneration in C. elegans models of Parkinson's and Machado-Joseph disease by rapeseed pomace extract supplementation. Front Neurosci 13, 1091. Polymeropoulos, M., Lavedan, C., Leroy, E., Ide, S., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W., Lazzarini, A., Duvoisin, R., Di Iorio, G., Golbe, L., Nussbaum, R., 1997. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276, 2045-2047. Poosti, M., Ramazanzadeh, B., Zebarjad, M., Javadzadeh, P., Naderinasab, M., Shakeri, M., 2013. Shear bond strength and antibacterial effects of orthodontic composite containing TiO2 nanoparticles. Eur J Orthod 35, 676-679. Priyadarsini, S., Mukherjee, S., Mishra, M., 2018. Nanoparticles used in dentistry: a review. J Oral Biol Craniofac Res 8, 58-67. Ramirez, A., Heimbach, A., Gründemann, J., Stiller, B., Hampshire, D., Cid, L., Goebel, I., Mubaidin, A., Wriekat, A., Roeper, J., Al-Din, A., Hillmer, A., Karsak, M., Liss, B., Woods, C., Behrens, M., Kubisch, C., 2006. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 38, 1184-1191. Ray, A., Martinez, B., Berkowitz, L., Caldwell, G., Caldwell, K., 2014. Mitochondrial dysfunction, oxidative stress, and neurodegeneration elicited by a bacterial metabolite in a C. elegans Parkinson's model. Cell Death Dis 5, e984. Roh, J., Kim, P., Kwon, J., 2018. Comparative study of oxidative stress caused by anthracene and alkyl-anthracenes in Caenorhabditis elegans. Environ Health Toxicol 33, e2018006. Ruszkiewicz, J., Pinkas, A., Miah, M., Weitz, R., Lawes, M., Akinyemi, A., Ijomone, O., Aschner, M., 2018. C. elegans as a model in developmental neurotoxicology. Toxicol Appl Pharmacol 354, 126-135. Ryan, B.J., Hoek, S., Fon, E.A., Wade-Martins, R., 2015. Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci 40, 200-210. Salehi, P., Babanouri, N., Roein-Peikar, M., Zare, F., 2018. Long-term antimicrobial assessment of orthodontic brackets coated with nitrogen-doped titanium dioxide against Streptococcus mutans. Prog Orthod 19, 35. Sawin, E., Ranganathan, R., Horvitz, H., 2000. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 26, 619-631. Schmalz, G., Hickel, R., van Landuyt, K., Reichl, F., 2017. Nanoparticles in dentistry. Dent Mater 33, 1298-1314. Settivari, R., VanDuyn, N., LeVora, J., Nass, R., 2013. The Nrf2/SKN-1-dependent glutathione S-transferase pi homologue GST-1 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of manganism. Neurotoxicology 38, 51-60. Shi, Y., Pan, T., Liao, V., 2016. Monascin from monascus-fermented products reduces oxidative stress and amyloid-beta toxicity via DAF-16/FOXO in Caenorhabditis elegans. J Agric Food Chem 64, 7114-7120. Shi, Y., Yu, C., Liao, V., Pan, T., 2012. Monascus-fermented dioscorea enhances oxidative stress resistance via DAF-16/FOXO in Caenorhabditis elegans. PLoS One 7, e39515. Shirai, R., Miura, T., Yoshida, A., Yoshino, F., Ito, T., Yoshinari, M., Yajima, Y., 2016. Antimicrobial effect of titanium dioxide after ultraviolet irradiation against periodontal pathogen. Dent Mater J 35, 511-516. Singleton, A., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, C., Cookson, M., Muenter, M., Baptista, M., Miller, D., Blancato, J., Hardy, J., Gwinn-Hardy, K., 2003. Alpha-Synuclein locus triplication causes Parkinson's disease. Science 302, 841. Spillantini, M., Schmidt, M., Lee, V., Trojanowski, J., Jakes, R., Goedert, M., 1997. Alpha-synuclein in Lewy bodies. Nature 388, 389-340. Sukhanova, A., Bozrova, S., Sokolov, P., Berestovoy, M., Karaulov, A., Nabiev, I., 2018. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res Lett 13, 44. Sun, J., Forster, A., Johnson, P., Eidelman, N., Quinn, G., Schumacher, G., Zhang, X., Wu, W., 2011. Improving performance of dental resins by adding titanium dioxide nanoparticles. Dent Mater 27, 972-982. Sun, J., Petersen, E., Watson, S., Sims, C., Kassman, A., Frukhtbeyn, S., Skrtic, D., Ok, M., Jacobs, D., Reipa, V., Ye, Q., Nelson, B., 2017. Biophysical characterization of functionalized titania nanoparticles and their application in dental adhesives. Acta Biomater 53, 585-597. Suttiponparnit, K., Jiang, J., Sahu, M., Suvachittanont, S., Charinpanitkul, T., Biswas, P., 2011. Role of surface area, primary particle size, and crystal phase on titanium dioxide nanoparticle dispersion properties. Nanoscale Res Lett 6, 27. Tang, T., Zhang, Z., Zhu, X., 2019. Toxic effects of TiO₂ NPs on zebrafish. Int J Environ Res Public Health 16, 523. Tetley, T., 2007. Health effects of nanomaterials. Biochem Soc Trans 35, 527-531. Tofaris, G., Kim, H., Hourez, R., Jung, J., Kim, K., Goldberg, A., 2011. Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway. Proc Natl Acad Sci USA 108, 17004-17009. Tong, T., Binh, C., Kelly, J., Gaillard, J., Gray, K., 2013. Cytotoxicity of commercial nano-TiO2 to Escherichia coli assessed by high-throughput screening: effects of environmental factors. Water Res 47, 2352-2362. Tseng, I., Yang, Y., Yu, C., Li, W., Liao, V., 2013. Phthalates induce neurotoxicity affecting locomotor and thermotactic behaviors and AFD neurons through oxidative stress in Caenorhabditis elegans. PLoS One 8, e82657. USEPA, 2002. Short-term methods for estimating the chronic toxicity of effluents and receiving waters to freshwater organisms. U.S. Environmental Protection Agency Washington, DC, 27. Vale, G., Mehennaoui, K., Cambier, S., Libralato, G., Jomini, S., Domingos, R., 2016. Manufactured nanoparticles in the aquatic environment-biochemical responses on freshwater organisms: a critical overview. Aquat Toxicol 170, 162-174. Valente, E., Abou-Sleiman, P., Caputo, V., Muqit, M., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A., Healy, D., Albanese, A., Nussbaum, R., González-Maldonado, R., Deller, T., Salvi, S., Cortelli, P., Gilks, W., Latchman, D., Harvey, R., Dallapiccola, B., Auburger, G., Wood, N., 2004. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304, 1158-1160. Vanduyn, N., Settivari, R., Wong, G., Nass, R., 2010. SKN-1/Nrf2 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of methylmercury toxicity. Toxicol Sci 118, 613-624. Walker, A., See, R., Batchelder, C., Kophengnavong, T., Gronniger, J., Shi, Y., Blackwell, T., 2000. A conserved transcription motif suggesting functional parallels between Caenorhabditis elegans SKN-1 and Cap'n'Collar-related basic leucine zipper proteins. J Biol Chem 275, 22166-22171. Wang, Q., Zou, M., 2018. Measurement of reactive oxygen species (ROS) and mitochondrial ROS in AMPK knockout mice blood vessels. Methods Mol Biol 1732, 507-517. Wen, H., Gao, X., Qin, J., 2014. Probing the anti-aging role of polydatin in Caenorhabditis elegans on a chip. Integr Biol (Camb) 6, 35-43. Xie, H., Wu, J., 2016. Silica nanoparticles induce alpha-synuclein induction and aggregation in PC12-cells. Chem Biol Interact 258, 197-204. Yu, C., How, C., Liao, V., 2016. Arsenite exposure accelerates aging process regulated by the transcription factor DAF-16/FOXO in Caenorhabditis elegans. Chemosphere 150, 632-638. Zeng, X., Jia, J., Kwon, Y., Wang, S., Bai, J., 2014. The role of thioredoxin-1 in suppression of endoplasmic reticulum stress in Parkinson disease. Free Radic Biol Med 67, 10-18. Zhang, Z., Li, G., Szeto, S., Chong, C., Quan, Q., Huang, C., Cui, W., Guo, B., Wang, Y., Han, Y., Michael Siu, K., Yuen Lee, S., Chu, I., 2015. Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease. Free Radic Biol Med 84, 331-343. Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R., Calne, D., Stoessl, A., Pfeiffer, R., Patenge, N., Carbajal, I., Vieregge, P., Asmus, F., Müller-Myhsok, B., Dickson, D., Meitinger, T., Strom, T., Wszolek, Z., Gasser, T., 2004. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601-607. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74982 | - |
dc.description.abstract | 研究目的 奈米二氧化鈦 (titanium dioxide nanoparticles, TiO2-NPs) 被廣泛應用於牙科材料中,具有良好的生物相容性以及抗菌能力。儘管TiO2-NPs在生醫領域已有許多研究,但TiO2-NPs對生物體之毒性效應並未明確,值得注意的是應用於牙科醫療的TiO2-NPs 可能會增加人體暴露於TiO2-NPs的風險。TiO2-NPs能成功穿過血腦屏障進入腦部,卻鮮少有研究探討TiO2-NPs與帕金森氏症之間的關係。本研究的目的在於探討TiO2-NPs造成帕金森氏症的可能風險。 研究程序及方法 利用基因轉殖之秀麗隱桿線蟲 (Caenorhabditis elegans, C. elegans) NL5901以及 BZ555評估長期暴露於TiO2-NPs 是否會使前突觸蛋白累積、多巴胺神經受損。透過分析C. elegans體內氧化壓力 (reactive oxidative stress, ROS) 以及多巴胺相關行為模式分析評估TiO2-NPs是否對C. elegans產生不良影響,並透過即時定量聚合酶連鎖反應 (qRT-PCR) 分析轉錄因子SKN-1的表達量。最後透過RNA干擾 (RNA interference, RNAi) 的技術了解TiO2-NPs、SKN-1以及帕金森氏症的交互作用以及其作用機轉。 結果 研究結果指出,長期暴露於低濃度1 µg/mL TiO2-NPs會顯著提升NL5901體內前突觸蛋白濃度,並使BZ555的多巴胺神經不正常百分比達16%,顯示長期暴露TiO2-NPs會對多巴胺神經造成損傷。體內氧化壓力分析中發現,長期暴露低濃度1 µg/mL TiO2-NPs會顯著提升BZ555體內ROS水平1.3倍。進一步的多巴胺相關行為模式分析發現,暴露於10 µg/mL TiO2-NPs其每20秒身體擺動次數相較於控制組會顯著減少30%,此結果代表暴露於TiO2-NPs影響多巴胺神經正常功能,影響C. elegans行為模式。在氧化壓力相關的轉錄因子SKN-1的RT-qPCR分析中,結果發現在1 µg/mL TiO2-NPs的濃度下,SKN-1以及其下游基因GST-38, GCS-1表現量顯著提升約2倍。在RNAi的實驗中發現,1 µg/mL TiO2-NPs的暴露濃度抑制SKN-1轉錄因子且會更顯著增加13% C. elegans多巴胺神經不正常比例,表示SKN-1在對抗TiO2-NPs產生的氧化壓力扮演重要角色。 結論 本研究結果顯示,在模式生物秀麗隱桿線蟲中,長期暴露於1 µg/mL TiO2-NPs會透過前突觸蛋白以及細胞內ROS累積,造成多巴胺神經損傷影響到其正常功能,進而可能造成帕金森氏症。TiO2-NPs的毒性效應和SKN-1 pathway相關,因此可以推斷SKN-1在保護TiO2-NPs所引起之帕金森氏症病徵中扮演重要角色。 | zh_TW |
dc.description.abstract | Objective Titanium dioxide nanoparticles (TiO2-NPs) are widely used in nowadays dental ma-terial with good biocompatibility and anti-bacteria effects. Despite many studies for TiO2-NPs in biomedical fields, the toxicity of TiO2-NPs to organisms was still unclear. In particular, the TiO2-NPs used in dental materials might potentially increase potential risk to human. TiO2-NPs could penetrate through the blood-brain-barrier (BBB), however, studies on the relationship between TiO2-NPs and Parkinson’s disease (PD) are limited. Herein, the purpose of this study was to evaluate the possible risk of PD by TiO2-NPs and its possible underlying mechanisms Materials and methods The transgenic strains of Caenorhabditis elegans (C. elegans) NL5901 and BZ555 were used to evaluate whether long-term exposure to TiO2-NPs results in α-synuclein accumulation, dopamine neuron damage or not. The effects of TiO2-NPs were further explored on C. elegans through intracellular ROS analysis and dopamine-related behavior analysis. In addition, qRT-PCR was performed to examine the mRNA levels of SKN-1 and its downstream genes. Finally, RNA interference technique was used to explore the association between SKN-1 and PD. Results The results showed that long-term exposure to TiO2-NPs (1 µg/mL) significantly increased α-synuclein level in NL5901 up to 10%, and enhanced dopamine neuron ab-normality in BZ555 around 16%. In addition, long-term exposure to 1 µg/mL TiO2-NPs significantly elevated the ROS level by 1.3 folds comparing to the unexposed control. Further dopamine neuron-related behavior analysis found that under 10 µg/mL of TiO2-NPs exposure, the body bending of C. elegans significantly reduced by 30%, com-pared with the unexposed control. This suggests that TiO2-NPs exposure affects the nor-mal function of dopamine neuron, leading to the behavior change of C. elegans. Moreover, TiO2-NPs significantly increased the mRNA levels of SKN-1 and its downstream gene, GST-38 and GCS-1. Furthermore, under TiO2-NPs (1 µg/mL) exposure, the dopamine neuron abnormality was further significantly increased 13% compared with the vector control after skn-1 knockdown, suggesting the vital role of SKN-1 on PD upon long-term TiO2-NPs exposure. Conclusion Results of this study showed that long-term exposure to 1 µg/mL TiO2-NPs in-creased accumulation of α-synuclein, and intracellular ROS, and caused dopamine neu-rons damage. The damaged dopamine neurons affected the normal function of dopamine neurons, leading to Parkinson's symptoms in C. elegans model. This study showed that the toxicity of TiO2-NPs was associated with the SKN-1 pathway, indicating that SKN-1 played an important role in protecting dopamine neurons against ROS caused by TiO2-NPs. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T09:11:55Z (GMT). No. of bitstreams: 1 U0001-3101202114501300.pdf: 4581509 bytes, checksum: a575f145b5bb98c2222c870e6019ef6d (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 口試委員審定書...................................................................i 致謝...........................................................................ii 中文摘要......................................................................iii 英文摘要Abstract................................................................v 1 研究動機......................................................................1 2 文獻回顧與研究目的..............................................................2 2.1牙科材料中的奈米二氧化鈦........................................................2 2.2 奈米二氧化鈦之毒性............................................................2 2.3 帕金森氏症...................................................................3 2.4 秀麗隱桿線蟲C. elegans 做為生物醫學及毒理學研究之模式生物..........................4 2.5 研究目的....................................................................5 3 材料與方法.....................................................................7 3.1 實驗架構與流程圖..............................................................7 3.2 實驗藥品....................................................................7 3.3 TiO2-NPs的特性分析...........................................................7 3.4 實驗生物與培養條件............................................................8 3.5 前突觸蛋白螢光定量分析.........................................................9 3.6 多巴胺神經螢光定性分析.........................................................9 3.7 體內ROS螢光定量分析...........................................................9 3.8 多巴胺相關行為模式分析........................................................10 3.9 即時定量聚合酶鏈鎖反應........................................................10 3.10 RNA干擾測試...............................................................11 3.11 統計分析..................................................................11 4 結果與討論....................................................................12 4.1 TiO2-NPs在EPA溶液中可以有效維持奈米尺度........................................12 4.2 TiO2-NPs使NL5901前突觸蛋白累積提升...........................................12 4.3 TiO2-NPs使BZ555多巴胺神經受損................................................13 4.4 TiO2-NPs使BZ555體內ROS上升..................................................14 4.5 多巴胺神經受損使BZ555出現行為模式改變..........................................15 4.6 daf-16, skn-1, gst-38, gcs-1在BZ555暴露於TiO2-NPs時表達量提升................16 4.7 SKN-1在BZ555多巴胺神經抵抗TiO2-NPs毒性時扮演重要角色............................18 5 結論.........................................................................19 6 未來展望.....................................................................20 附圖...........................................................................21 圖1...........................................................................21 圖2...........................................................................22 圖3...........................................................................23 圖4...........................................................................24 圖5...........................................................................25 圖6...........................................................................26 圖7...........................................................................27 圖8...........................................................................28 圖9...........................................................................29 圖10..........................................................................30 圖11..........................................................................31 圖12..........................................................................32 圖13..........................................................................33 圖14..........................................................................34 附表...........................................................................35 表1...........................................................................35 表2...........................................................................36 參考文獻.......................................................................37 | |
dc.language.iso | zh-TW | |
dc.title | 探討應用於牙科醫療之奈米二氧化鈦粒子長期暴露對於帕金森氏症的影響及其作用機轉 | zh_TW |
dc.title | Long term exposure to titanium dioxide nanoparticles used in dental practice on Parkinson’s disease and its underlying mechanisms | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 廖秀娟(Hsiu-Chuan Liao) | |
dc.contributor.oralexamcommittee | 張瑞青(Zwei-Chieng Chang) | |
dc.subject.keyword | 奈米二氧化鈦,帕金森氏症,牙科材料,長期暴露,秀麗隱桿線蟲,SKN-1, | zh_TW |
dc.subject.keyword | titanium dioxide nanoparticle,Parkinson’s disease,dental material,long-term exposure,Caenorhabditis elegans,SKN-1, | en |
dc.relation.page | 43 | |
dc.identifier.doi | 10.6342/NTU202100289 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2021-03-24 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
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