帕金森氏症小鼠發病前腸道菌的長期研究

Feng Liang; 梁風

請用此 Handle URI 來引用此文件： http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79572

完整後設資料紀錄

DC 欄位	值	語言
dc.contributor.advisor	陳示國(Shih-Kuo Chen)
dc.contributor.author	Feng Liang	en
dc.contributor.author	梁風	zh_TW
dc.date.accessioned	2022-11-23T09:04:02Z	-
dc.date.available	2021-11-08
dc.date.available	2022-11-23T09:04:02Z	-
dc.date.copyright	2021-11-08
dc.date.issued	2021
dc.date.submitted	2021-09-17
dc.identifier.citation	Uncategorized References Aho, V. T. E., Pereira, P. A. B., Voutilainen, S., Paulin, L., Pekkonen, E., Auvinen, P., Scheperjans, F. (2019). Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression. EBioMedicine, 44, 691-707. https://doi.org/10.1016/j.ebiom.2019.05.064 Balsalobre, A., Damiola, F., Schibler, U. (1998). A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell, 93(6), 929-937. https://doi.org/10.1016/s0092-8674(00)81199-x Beach, T. G., Adler, C. H., Lue, L., Sue, L. I., Bachalakuri, J., Henry-Watson, J., Sasse, J., Boyer, S., Shirohi, S., Brooks, R., Eschbacher, J., White, C. L., 3rd, Akiyama, H., Caviness, J., Shill, H. A., Connor, D. J., Sabbagh, M. N., Walker, D. G., Arizona Parkinson's Disease, C. (2009). Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol, 117(6), 613-634. https://doi.org/10.1007/s00401-009-0538-8 Beli, E., Prabakaran, S., Krishnan, P., Evans-Molina, C., Grant, M. B. (2019). Loss of Diurnal Oscillatory Rhythms in Gut Microbiota Correlates with Changes in Circulating Metabolites in Type 2 Diabetic db/db Mice. Nutrients, 11(10). https://doi.org/10.3390/nu11102310 Bencsik, A., Muselli, L., Leboidre, M., Lakhdar, L., Baron, T. (2014). Early and persistent expression of phosphorylated alpha-synuclein in the enteric nervous system of A53T mutant human alpha-synuclein transgenic mice. J Neuropathol Exp Neurol, 73(12), 1144-1151. https://doi.org/10.1097/NEN.0000000000000137 Berson, D. M., Dunn, F. A., Takao, M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science, 295(5557), 1070-1073. https://doi.org/10.1126/science.1067262 Bogiatzi, C., Gloor, G., Allen-Vercoe, E., Reid, G., Wong, R. G., Urquhart, B. L., Dinculescu, V., Ruetz, K. N., Velenosi, T. J., Pignanelli, M., Spence, J. D. (2018). Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis, 273, 91-97. https://doi.org/10.1016/j.atherosclerosis.2018.04.015 Bonaz, B., Bazin, T., Pellissier, S. (2018). The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci, 12, 49. https://doi.org/10.3389/fnins.2018.00049 Bourassa, M. W., Alim, I., Bultman, S. J., Ratan, R. R. (2016). Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? Neurosci Lett, 625, 56-63. https://doi.org/10.1016/j.neulet.2016.02.009 Braak, H., de Vos, R. A., Bohl, J., Del Tredici, K. (2006). Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett, 396(1), 67-72. https://doi.org/10.1016/j.neulet.2005.11.012 Braak, H., Del Tredici, K. (2017). Neuropathological Staging of Brain Pathology in Sporadic Parkinson's disease: Separating the Wheat from the Chaff. J Parkinsons Dis, 7(s1), S71-S85. https://doi.org/10.3233/JPD-179001 Braak, H., Del Tredici, K., Rub, U., de Vos, R. A., Jansen Steur, E. N., Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging, 24(2), 197-211. https://doi.org/10.1016/s0197-4580(02)00065-9 Braak, H., Sastre, M., Bohl, J. R., de Vos, R. A., Del Tredici, K. (2007). Parkinson's disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons. Acta Neuropathol, 113(4), 421-429. https://doi.org/10.1007/s00401-007-0193-x Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A, 108(38), 16050-16055. https://doi.org/10.1073/pnas.1102999108 Breit, S., Kupferberg, A., Rogler, G., Hasler, G. (2018). Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry, 9, 44. https://doi.org/10.3389/fpsyt.2018.00044 Buffington, S. A., Di Prisco, G. V., Auchtung, T. A., Ajami, N. J., Petrosino, J. F., Costa-Mattioli, M. (2016). Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell, 165(7), 1762-1775. https://doi.org/10.1016/j.cell.2016.06.001 Buhr, E. D., Vemaraju, S., Diaz, N., Lang, R. A., Van Gelder, R. N. (2019). Neuropsin (OPN5) Mediates Local Light-Dependent Induction of Circadian Clock Genes and Circadian Photoentrainment in Exposed Murine Skin. Curr Biol, 29(20), 3478-3487 e3474. https://doi.org/10.1016/j.cub.2019.08.063 Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Pena, A. G., Goodrich, J. K., Gordon, J. I., Huttley, G. A., Kelley, S. T., Knights, D., Koenig, J. E., Ley, R. E., Lozupone, C. A., McDonald, D., Muegge, B. D., Pirrung, M., Reeder, J., Sevinsky, J. R., Turnbaugh, P. J., Walters, W. A., Widmann, J., Yatsunenko, T., Zaneveld, J., Knight, R. (2010). QIIME allows analysis of high-throughput community sequencing data. Nat Methods, 7(5), 335-336. https://doi.org/10.1038/nmeth.f.303 Careaga, M., Rogers, S., Hansen, R. L., Amaral, D. G., Van de Water, J., Ashwood, P. (2017). Immune Endophenotypes in Children With Autism Spectrum Disorder. Biol Psychiatry, 81(5), 434-441. https://doi.org/10.1016/j.biopsych.2015.08.036 Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., Bianchetti, A., Volta, G. D., Turla, M., Cotelli, M. S., Gennuso, M., Prelle, A., Zanetti, O., Lussignoli, G., Mirabile, D., Bellandi, D., Gentile, S., Belotti, G., Villani, D., Harach, T., Bolmont, T., Padovani, A., Boccardi, M., Frisoni, G. B., Group, I.-F. (2017). Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging, 49, 60-68. https://doi.org/10.1016/j.neurobiolaging.2016.08.019 Chen, H., Cho, K. S., Vu, T. H. K., Shen, C. H., Kaur, M., Chen, G., Mathew, R., McHam, M. L., Fazelat, A., Lashkari, K., Au, N. P. B., Tse, J. K. Y., Li, Y., Yu, H., Yang, L., Stein-Streilein, J., Ma, C. H. E., Woolf, C. J., Whary, M. T., Jager, M. J., Fox, J. G., Chen, J., Chen, D. F. (2018). Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma. Nat Commun, 9(1), 3209. https://doi.org/10.1038/s41467-018-05681-9 Claesson, M. J., Wang, Q., O'Sullivan, O., Greene-Diniz, R., Cole, J. R., Ross, R. P., O'Toole, P. W. (2010). Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res, 38(22), e200. https://doi.org/10.1093/nar/gkq873 Clarke, G., Grenham, S., Scully, P., Fitzgerald, P., Moloney, R. D., Shanahan, F., Dinan, T. G., Cryan, J. F. (2013). The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry, 18(6), 666-673. https://doi.org/10.1038/mp.2012.77 Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., Dinan, T. G. (2014). Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol, 28(8), 1221-1238. https://doi.org/10.1210/me.2014-1108 Comeau, A. M., Douglas, G. M., Langille, M. G. (2017). Microbiome Helper: a Custom and Streamlined Workflow for Microbiome Research. mSystems, 2(1). https://doi.org/10.1128/mSystems.00127-16 Cryan, J. F., O'Riordan, K. J., Sandhu, K., Peterson, V., Dinan, T. G. (2020). The gut microbiome in neurological disorders. Lancet Neurol, 19(2), 179-194. https://doi.org/10.1016/S1474-4422(19)30356-4 Daniel, H., Gholami, A. M., Berry, D., Desmarchelier, C., Hahne, H., Loh, G., Mondot, S., Lepage, P., Rothballer, M., Walker, A., Bohm, C., Wenning, M., Wagner, M., Blaut, M., Schmitt-Kopplin, P., Kuster, B., Haller, D., Clavel, T. (2014). High-fat diet alters gut microbiota physiology in mice. ISME J, 8(2), 295-308. https://doi.org/10.1038/ismej.2013.155 De Lazzari, F., Bisaglia, M., Zordan, M. A., Sandrelli, F. (2018). Circadian Rhythm Abnormalities in Parkinson's Disease from Humans to Flies and Back. Int J Mol Sci, 19(12). https://doi.org/10.3390/ijms19123911 De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Backhed, F., Mithieux, G. (2014). Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell, 156(1-2), 84-96. https://doi.org/10.1016/j.cell.2013.12.016 Del Tredici, K., Braak, H. (2008). A not entirely benign procedure: progression of Parkinson's disease. Acta Neuropathol, 115(4), 379-384. https://doi.org/10.1007/s00401-008-0355-5 Dorsey, E. R., Sherer, T., Okun, M. S., Bloem, B. R. (2018). The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis, 8(s1), S3-S8. https://doi.org/10.3233/JPD-181474 Duffy, J. F., Wright, K. P., Jr. (2005). Entrainment of the human circadian system by light. J Biol Rhythms, 20(4), 326-338. https://doi.org/10.1177/0748730405277983 Edwards, L. L., Quigley, E. M., Pfeiffer, R. F. (1992). Gastrointestinal dysfunction in Parkinson's disease: frequency and pathophysiology. Neurology, 42(4), 726-732. https://doi.org/10.1212/wnl.42.4.726 Eelderink-Chen, Z., Bosman, J., Sartor, F., Dodd, A. N., Kovacs, A. T., Merrow, M. (2021). A circadian clock in a nonphotosynthetic prokaryote. Sci Adv, 7(2). https://doi.org/10.1126/sciadv.abe2086 Forsyth, C. B., Shannon, K. M., Kordower, J. H., Voigt, R. M., Shaikh, M., Jaglin, J. A., Estes, J. D., Dodiya, H. B., Keshavarzian, A. (2011). Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One, 6(12), e28032. https://doi.org/10.1371/journal.pone.0028032 Gekakis, N., Staknis, D., Nguyen, H. B., Davis, F. C., Wilsbacher, L. D., King, D. P., Takahashi, J. S., Weitz, C. J. (1998). Role of the CLOCK protein in the mammalian circadian mechanism. Science, 280(5369), 1564-1569. https://doi.org/10.1126/science.280.5369.1564 Golubeva, A. V., Joyce, S. A., Moloney, G., Burokas, A., Sherwin, E., Arboleya, S., Flynn, I., Khochanskiy, D., Moya-Perez, A., Peterson, V., Rea, K., Murphy, K., Makarova, O., Buravkov, S., Hyland, N. P., Stanton, C., Clarke, G., Gahan, C. G. M., Dinan, T. G., Cryan, J. F. (2017). Microbiota-related Changes in Bile Acid Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism. EBioMedicine, 24, 166-178. https://doi.org/10.1016/j.ebiom.2017.09.020 Hasegawa, S., Goto, S., Tsuji, H., Okuno, T., Asahara, T., Nomoto, K., Shibata, A., Fujisawa, Y., Minato, T., Okamoto, A., Ohno, K., Hirayama, M. (2015). Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease. PLoS One, 10(11), e0142164. https://doi.org/10.1371/journal.pone.0142164 Hattar, S., Liao, H. W., Takao, M., Berson, D. M., Yau, K. W. (2002). Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science, 295(5557), 1065-1070. https://doi.org/10.1126/science.1069609 Hau, M., Gwinner, E. (1996). Food as a circadian Zeitgeber for house sparrows: the effect of different food access durations. J Biol Rhythms, 11(3), 196-207. https://doi.org/10.1177/074873049601100302 Henke, M. T., Kenny, D. J., Cassilly, C. D., Vlamakis, H., Xavier, R. J., Clardy, J. (2019). Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A, 116(26), 12672-12677. https://doi.org/10.1073/pnas.1904099116 Hilton, D., Stephens, M., Kirk, L., Edwards, P., Potter, R., Zajicek, J., Broughton, E., Hagan, H., Carroll, C. (2014). Accumulation of alpha-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease. Acta Neuropathol, 127(2), 235-241. https://doi.org/10.1007/s00401-013-1214-6 Hogenesch, J. B., Gu, Y. Z., Jain, S., Bradfield, C. A. (1998). The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci U S A, 95(10), 5474-5479. https://doi.org/10.1073/pnas.95.10.5474 Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., Patterson, P. H., Mazmanian, S. K. (2013). Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 155(7), 1451-1463. https://doi.org/10.1016/j.cell.2013.11.024 Hughes, M. E., Hogenesch, J. B., Kornacker, K. (2010). JTK_CYCLE: an efficient nonparametric algorithm for detecting rhythmic components in genome-scale data sets. J Biol Rhythms, 25(5), 372-380. https://doi.org/10.1177/0748730410379711 Jia, H. M., Li, Q., Zhou, C., Yu, M., Yang, Y., Zhang, H. W., Ding, G., Shang, H., Zou, Z. M. (2016). Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression. Sci Rep, 6, 23441. https://doi.org/10.1038/srep23441 Jilge, B. (1992). Restricted feeding: a nonphotic zeitgeber in the rabbit. Physiol Behav, 51(1), 157-166. https://doi.org/10.1016/0031-9384(92)90218-q Johnson, C. H., Stewart, P. L., Egli, M. (2011). The cyanobacterial circadian system: from biophysics to bioevolution. Annu Rev Biophys, 40, 143-167. https://doi.org/10.1146/annurev-biophys-042910-155317 Kallaur, A. P., Reiche, E. M. V., Oliveira, S. R., Simao, A. N. C., Pereira, W., Alfieri, D. F., Flauzino, T., Proenca, C. M., Lozovoy, M. A. B., Kaimen-Maciel, D. R., Maes, M. (2017). Genetic, Immune-Inflammatory, and Oxidative Stress Biomarkers as Predictors for Disability and Disease Progression in Multiple Sclerosis. Mol Neurobiol, 54(1), 31-44. https://doi.org/10.1007/s12035-015-9648-6 Kang, D. W., Adams, J. B., Gregory, A. C., Borody, T., Chittick, L., Fasano, A., Khoruts, A., Geis, E., Maldonado, J., McDonough-Means, S., Pollard, E. L., Roux, S., Sadowsky, M. J., Lipson, K. S., Sullivan, M. B., Caporaso, J. G., Krajmalnik-Brown, R. (2017). Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome, 5(1), 10. https://doi.org/10.1186/s40168-016-0225-7 Kato, K., Odamaki, T., Mitsuyama, E., Sugahara, H., Xiao, J. Z., Osawa, R. (2017). Age-Related Changes in the Composition of Gut Bifidobacterium Species. Curr Microbiol, 74(8), 987-995. https://doi.org/10.1007/s00284-017-1272-4 Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., Shannon, K. M. (2015). Colonic bacterial composition in Parkinson's disease. Mov Disord, 30(10), 1351-1360. https://doi.org/10.1002/mds.26307 Kim, S., Kim, H., Yim, Y. S., Ha, S., Atarashi, K., Tan, T. G., Longman, R. S., Honda, K., Littman, D. R., Choi, G. B., Huh, J. R. (2017). Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature, 549(7673), 528-532. https://doi.org/10.1038/nature23910 Kim, S., Kwon, S. H., Kam, T. I., Panicker, N., Karuppagounder, S. S., Lee, S., Lee, J. H., Kim, W. R., Kook, M., Foss, C. A., Shen, C., Lee, H., Kulkarni, S., Pasricha, P. J., Lee, G., Pomper, M. G., Dawson, V. L., Dawson, T. M., Ko, H. S. (2019). Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron, 103(4), 627-641 e627. https://doi.org/10.1016/j.neuron.2019.05.035 Kornmann, B., Schaad, O., Bujard, H., Takahashi, J. S., Schibler, U. (2007). System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol, 5(2), e34. https://doi.org/10.1371/journal.pbio.0050034 Korshunov, K. S., Blakemore, L. J., Trombley, P. Q. (2017). Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System. Front Cell Neurosci, 11, 91. https://doi.org/10.3389/fncel.2017.00091 Kuang, Z., Wang, Y., Li, Y., Ye, C., Ruhn, K. A., Behrendt, C. L., Olson, E. N., Hooper, L. V. (2019). The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science, 365(6460), 1428-1434. https://doi.org/10.1126/science.aaw3134 Kudo, T., Loh, D. H., Truong, D., Wu, Y., Colwell, C. S. (2011). Circadian dysfunction in a mouse model of Parkinson's disease. Exp Neurol, 232(1), 66-75. https://doi.org/10.1016/j.expneurol.2011.08.003 Kume, K., Zylka, M. J., Sriram, S., Shearman, L. P., Weaver, D. R., Jin, X., Maywood, E. S., Hastings, M. H., Reppert, S. M. (1999). mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell, 98(2), 193-205. https://doi.org/10.1016/s0092-8674(00)81014-4 Leone, V., Gibbons, S. M., Martinez, K., Hutchison, A. L., Huang, E. Y., Cham, C. M., Pierre, J. F., Heneghan, A. F., Nadimpalli, A., Hubert, N., Zale, E., Wang, Y., Huang, Y., Theriault, B., Dinner, A. R., Musch, M. W., Kudsk, K. A., Prendergast, B. J., Gilbert, J. A., Chang, E. B. (2015). Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe, 17(5), 681-689. https://doi.org/10.1016/j.chom.2015.03.006 Ley, R. E., Peterson, D. A., Gordon, J. I. (2006). Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell, 124(4), 837-848. https://doi.org/10.1016/j.cell.2006.02.017 Li, Q., Han, Y., Dy, A. B. C., Hagerman, R. J. (2017). The Gut Microbiota and Autism Spectrum Disorders. Front Cell Neurosci, 11, 120. https://doi.org/10.3389/fncel.2017.00120 Li, S., Wang, Y., Wang, F., Hu, L. F., Liu, C. F. (2017). A New Perspective for Parkinson's Disease: Circadian Rhythm. Neurosci Bull, 33(1), 62-72. https://doi.org/10.1007/s12264-016-0089-7 Liang, X., Bushman, F. D., FitzGerald, G. A. (2015). Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc Natl Acad Sci U S A, 112(33), 10479-10484. https://doi.org/10.1073/pnas.1501305112 Macleod, A. D., Taylor, K. S., Counsell, C. E. (2014). Mortality in Parkinson's disease: a systematic review and meta-analysis. Mov Disord, 29(13), 1615-1622. https://doi.org/10.1002/mds.25898 Mantovani, S., Smith, S. S., Gordon, R., O'Sullivan, J. D. (2018). An overview of sleep and circadian dysfunction in Parkinson's disease. J Sleep Res, 27(3), e12673. https://doi.org/10.1111/jsr.12673 Mrosovsky, N. (1988). Phase response curves for social entrainment. J Comp Physiol A, 162(1), 35-46. https://doi.org/10.1007/bf01342701 Mukherji, A., Kobiita, A., Ye, T., Chambon, P. (2013). Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell, 153(4), 812-827. https://doi.org/10.1016/j.cell.2013.04.020 Nishiwaki, H., Ito, M., Ishida, T., Hamaguchi, T., Maeda, T., Kashihara, K., Tsuboi, Y., Ueyama, J., Shimamura, T., Mori, H., Kurokawa, K., Katsuno, M., Hirayama, M., Ohno, K. (2020). Meta-Analysis of Gut Dysbiosis in Parkinson's Disease. Mov Disord, 35(9), 1626-1635. https://doi.org/10.1002/mds.28119 Noorian, A. R., Rha, J., Annerino, D. M., Bernhard, D., Taylor, G. M., Greene, J. G. (2012). Alpha-synuclein transgenic mice display age-related slowing of gastrointestinal motility associated with transgene expression in the vagal system. Neurobiol Dis, 48(1), 9-19. https://doi.org/10.1016/j.nbd.2012.06.005 Ochoa-Reparaz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Foureau, D. M., Haque-Begum, S., Kasper, L. H. (2009). Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol, 183(10), 6041-6050. https://doi.org/10.4049/jimmunol.0900747 Odamaki, T., Kato, K., Sugahara, H., Hashikura, N., Takahashi, S., Xiao, J. Z., Abe, F., Osawa, R. (2016). Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol, 16, 90. https://doi.org/10.1186/s12866-016-0708-5 Okamura, H., Miyake, S., Sumi, Y., Yamaguchi, S., Yasui, A., Muijtjens, M., Hoeijmakers, J. H., van der Horst, G. T. (1999). Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Science, 286(5449), 2531-2534. https://doi.org/10.1126/science.286.5449.2531 Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., Hsiao, E. Y. (2018). The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell, 173(7), 1728-1741 e1713. https://doi.org/10.1016/j.cell.2018.04.027 Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., Le Chatelier, E., Levenez, F., Dore, J., Mattila, I., Plichta, D. R., Poho, P., Hellgren, L. I., Arumugam, M., Sunagawa, S., Vieira-Silva, S., Jorgensen, T., Holm, J. B., Trost, K., Meta, H. I. T. C., Kristiansen, K., Brix, S., Raes, J., Wang, J., Hansen, T., Bork, P., Brunak, S., Oresic, M., Ehrlich, S. D., Pedersen, O. (2016). Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, 535(7612), 376-381. https://doi.org/10.1038/nature18646 Petrov, V. A., Saltykova, I. V., Zhukova, I. A., Alifirova, V. M., Zhukova, N. G., Dorofeeva, Y. B., Tyakht, A. V., Kovarsky, B. A., Alekseev, D. G., Kostryukova, E. S., Mironova, Y. S., Izhboldina, O. P., Nikitina, M. A., Perevozchikova, T. V., Fait, E. A., Babenko, V. V., Vakhitova, M. T., Govorun, V. M., Sazonov, A. E. (2017). Analysis of Gut Microbiota in Patients with Parkinson's Disease. Bull Exp Biol Med, 162(6), 734-737. https://doi.org/10.1007/s10517-017-3700-7 Preitner, N., Damiola, F., Lopez-Molina, L., Zakany, J., Duboule, D., Albrecht, U., Schibler, U. (2002). The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell, 110(2), 251-260. https://doi.org/10.1016/s0092-8674(02)00825-5 Ray, N. J., Jenkinson, N., Wang, S., Holland, P., Brittain, J. S., Joint, C., Stein, J. F., Aziz, T. (2008). Local field potential beta activity in the subthalamic nucleus of patients with Parkinson's disease is associated with improvements in bradykinesia after dopamine and deep brain stimulation. Exp Neurol, 213(1), 108-113. https://doi.org/10.1016/j.expneurol.2008.05.008 Reitmeier, S., Kiessling, S., Clavel, T., List, M., Almeida, E. L., Ghosh, T. S., Neuhaus, K., Grallert, H., Linseisen, J., Skurk, T., Brandl, B., Breuninger, T. A., Troll, M., Rathmann, W., Linkohr, B., Hauner, H., Laudes, M., Franke, A., Le Roy, C. I., Bell, J. T., Spector, T., Baumbach, J., O'Toole, P. W., Peters, A., Haller, D. (2020). Arrhythmic Gut Microbiome Signatures Predict Risk of Type 2 Diabetes. Cell Host Microbe, 28(2), 258-272 e256. https://doi.org/10.1016/j.chom.2020.06.004 Reppert, S. M., Weaver, D. R. (2002). Coordination of circadian timing in mammals. Nature, 418(6901), 935-941. https://doi.org/10.1038/nature00965 Richard, C., Wadowski, M., Goruk, S., Cameron, L., Sharma, A. M., Field, C. J. (2017). Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy. BMJ Open Diabetes Res Care, 5(1), e000379. https://doi.org/10.1136/bmjdrc-2016-000379 Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., Muehlbauer, M. J., Ilkayeva, O., Semenkovich, C. F., Funai, K., Hayashi, D. K., Lyle, B. J., Martini, M. C., Ursell, L. K., Clemente, J. C., Van Treuren, W., Walters, W. A., Knight, R., Newgard, C. B., Heath, A. C., Gordon, J. I. (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341(6150), 1241214. https://doi.org/10.1126/science.1241214 Rios-Covian, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., de Los Reyes-Gavilan, C. G., Salazar, N. (2016). Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health. Front Microbiol, 7, 185. https://doi.org/10.3389/fmicb.2016.00185 Rodrigues-Amorim, D., Rivera-Baltanas, T., Regueiro, B., Spuch, C., de Las Heras, M. E., Vazquez-Noguerol Mendez, R., Nieto-Araujo, M., Barreiro-Villar, C., Olivares, J. M., Agis-Balboa, R. C. (2018). The role of the gut microbiota in schizophrenia: Current and future perspectives. World J Biol Psychiatry, 19(8), 571-585. https://doi.org/10.1080/15622975.2018.1433878 Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., Chesselet, M. F., Keshavarzian, A., Shannon, K. M., Krajmalnik-Brown, R., Wittung-Stafshede, P., Knight, R., Mazmanian, S. K. (2016). Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell, 167(6), 1469-1480 e1412. https://doi.org/10.1016/j.cell.2016.11.018 Savica, R., Bower, J. H., Maraganore, D. M., Grossardt, B. R., Rocca, W. A. (2009). Bell's palsy preceding Parkinson's disease: a case-control study. Mov Disord, 24(10), 1530-1533. https://doi.org/10.1002/mds.22616 Savica, R., Rocca, W. A., Ahlskog, J. E. (2010). When does Parkinson disease start? Arch Neurol, 67(7), 798-801. https://doi.org/10.1001/archneurol.2010.135 Schirmer, M., Franzosa, E. A., Lloyd-Price, J., McIver, L. J., Schwager, R., Poon, T. W., Ananthakrishnan, A. N., Andrews, E., Barron, G., Lake, K., Prasad, M., Sauk, J., Stevens, B., Wilson, R. G., Braun, J., Denson, L. A., Kugathasan, S., McGovern, D. P. B., Vlamakis, H., Xavier, R. J., Huttenhower, C. (2018). Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol, 3(3), 337-346. https://doi.org/10.1038/s41564-017-0089-z Schretter, C. E., Vielmetter, J., Bartos, I., Marka, Z., Marka, S., Argade, S., Mazmanian, S. K. (2018). A gut microbial factor modulates locomotor behaviour in Drosophila. Nature, 563(7731), 402-406. https://doi.org/10.1038/s41586-018-0634-9 Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., Huttenhower, C. (2011). Metagenomic biomarker discovery and explanation. Genome Biol, 12(6), R60. https://doi.org/10.1186/gb-2011-12-6-r60 Sehadova, H., Glaser, F. T., Gentile, C., Simoni, A., Giesecke, A., Albert, J. T., Stanewsky, R. (2009). Temperature entrainment of Drosophila's circadian clock involves the gene nocte and signaling from peripheral sensory tissues to the brain. Neuron, 64(2), 251-266. https://doi.org/10.1016/j.neuron.2009.08.026 Shannon, K. M., Keshavarzian, A., Dodiya, H. B., Jakate, S., Kordower, J. H. (2012). Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord, 27(6), 716-719. https://doi.org/10.1002/mds.25020 Shearman, L. P., Sriram, S., Weaver, D. R., Maywood, E. S., Chaves, I., Zheng, B., Kume, K., Lee, C. C., van der Horst, G. T., Hastings, M. H., Reppert, S. M. (2000). Interacting molecular loops in the mammalian circadian clock. Science, 288(5468), 1013-1019. https://doi.org/10.1126/science.288.5468.1013 Shulman, J. M., De Jager, P. L., Feany, M. B. (2011). Parkinson's disease: genetics and pathogenesis. Annu Rev Pathol, 6, 193-222. https://doi.org/10.1146/annurev-pathol-011110-130242 Singh, V., Roth, S., Llovera, G., Sadler, R., Garzetti, D., Stecher, B., Dichgans, M., Liesz, A. (2016). Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke. J Neurosci, 36(28), 7428-7440. https://doi.org/10.1523/JNEUROSCI.1114-16.2016 Soares, N. M., Pereira, G. M., Altmann, V., de Almeida, R. M. M., Rieder, C. R. M. (2019). Cortisol levels, motor, cognitive and behavioral symptoms in Parkinson's disease: a systematic review. J Neural Transm (Vienna), 126(3), 219-232. https://doi.org/10.1007/s00702-018-1947-4 Stewart, C. J., Ajami, N. J., O'Brien, J. L., Hutchinson, D. S., Smith, D. P., Wong, M. C., Ross, M. C., Lloyd, R. E., Doddapaneni, H., Metcalf, G. A., Muzny, D., Gibbs, R. A., Vatanen, T., Huttenhower, C., Xavier, R. J., Rewers, M., Hagopian, W., Toppari, J., Ziegler, A. G., She, J. X., Akolkar, B., Lernmark, A., Hyoty, H., Vehik, K., Krischer, J. P., Petrosino, J. F. (2018). Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature, 562(7728), 583-588. https://doi.org/10.1038/s41586-018-0617-x Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., Kubo, C., Koga, Y. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol, 558(Pt 1), 263-275. https://doi.org/10.1113/jphysiol.2004.063388 Thaiss, C. A., Zeevi, D., Levy, M., Zilberman-Schapira, G., Suez, J., Tengeler, A. C., Abramson, L., Katz, M. N., Korem, T., Zmora, N., Kuperman, Y., Biton, I., Gilad, S., Harmelin, A., Shapiro, H., Halpern, Z., Segal, E., Elinav, E. (2014). Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell, 159(3), 514-529. https://doi.org/10.1016/j.cell.2014.09.048 Tilg, H. (2010). Obesity, metabolic syndrome, and microbiota: multiple interactions. J Clin Gastroenterol, 44 Suppl 1, S16-18. https://doi.org/10.1097/MCG.0b013e3181dd8b64 Uemura, N., Yagi, H., Uemura, M. T., Hatanaka, Y., Yamakado, H., Takahashi, R. (2018). Inoculation of alpha-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve. Mol Neurodegener, 13(1), 21. https://doi.org/10.1186/s13024-018-0257-5 Unger, M. M., Spiegel, J., Dillmann, K. U., Grundmann, D., Philippeit, H., Burmann, J., Fassbender, K., Schwiertz, A., Schafer, K. H. (2016). Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord, 32, 66-72. https://doi.org/10.1016/j.parkreldis.2016.08.019 Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol, 4(4), 623-632. https://doi.org/10.1038/s41564-018-0337-x Videnovic, A., Golombek, D. (2017). Circadian Dysregulation in Parkinson's Disease. Neurobiol Sleep Circadian Rhythms, 2, 53-58. https://doi.org/10.1016/j.nbscr.2016.11.001 Vitaterna, M. H., Selby, C. P., Todo, T., Niwa, H., Thompson, C., Fruechte, E. M., Hitomi, K., Thresher, R. J., Ishikawa, T., Miyazaki, J., Takahashi, J. S., Sancar, A. (1999). Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. Proc Natl Acad Sci U S A, 96(21), 12114-12119. https://doi.org/10.1073/pnas.96.21.12114 Wallen, Z. D., Appah, M., Dean, M. N., Sesler, C. L., Factor, S. A., Molho, E., Zabetian, C. P., Standaert, D. G., Payami, H. (2020). Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. NPJ Parkinsons Dis, 6, 11. https://doi.org/10.1038/s41531-020-0112-6 Willis, G. L. (2008). Parkinson's disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process. Rev Neurosci, 19(4-5), 245-316. https://doi.org/10.1515/revneuro.2008.19.4-5.245 Winer, D. A., Luck, H., Tsai, S., Winer, S. (2016). The Intestinal Immune System in Obesity and Insulin Resistance. Cell Metab, 23(3), 413-426. https://doi.org/10.1016/j.cmet.2016.01.003 Wu, G., Tang, W., He, Y., Hu, J., Gong, S., He, Z., Wei, G., Lv, L., Jiang, Y., Zhou, H., Ch………
dc.identifier.uri	http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79572	-
dc.description.abstract	帕金森氏症是最普遍的退化性神經疾病之一，其原因是α-突觸核蛋白不正常地堆積在神經細胞中(路易氏體)。帕金森氏症致病因素包括環境、基因背景甚至腸道菌的交互影響。研究顯示帕金森氏症患者的腸道菌會加重小鼠的運動功能障礙。然而在帕金森氏症中腸道菌是什麼時候以及如何發生變化是仍然未知。結合16S基因體定序分析以及運動行為測試，我們發現在過量表現變異人類α-突觸核蛋白帕金森氏症模型小鼠的腸道菌在成年時就已經發生腸道微生態失調，遠早於小鼠發病的年紀。另外，腸道菌的日夜週期性在帕金森氏症模型小鼠中也會漸漸地消失。由於紊亂的光週期如夜晚照光可以消弭腸道菌的週期性，在此研究中我們也證實當帕金森氏症模型小鼠暴露於夜晚低光的環境中運動行為會提早退化。這些研究顯示了生理時鐘-腸軸在帕金森氏症發病的影響，且可能提出一個影響病程的重要環境因素。	zh_TW
dc.description.provenance	Made available in DSpace on 2022-11-23T09:04:02Z (GMT). No. of bitstreams: 1 U0001-1609202116554500.pdf: 14225393 bytes, checksum: ac78c1a214572ad43994bd9ce2fc4329 (MD5) Previous issue date: 2021	en
dc.description.tableofcontents	"謝誌 ii 摘要 iii Abstract iv Contents v Chapter I Introduction 1 1.1 Parkinson’s disease 1 1.1.1 Overview of Parkinson’s disease 1 1.1.2 Braak hypothesis 2 1.1.2 Dysbiosis in Parkinson’s disease 3 1.2 Circadian rhythm 4 1.2.1 Overview of the circadian rhythm 4 1.2.2 Intracellular clock mechanism in the mouse 5 1.2.3 Peripheral clock 7 1.3 Gut microbiota 8 1.3.1 General description of gut microbiota 8 1.3.2 Diurnal oscillatory rhythms of gut microbiota 9 1.3.3 Gut-brain axis 11 Statement of Purpose 13 Chapter II Materials and Methods 14 2.1 Animals 14 2.2 Experimental design 14 2.2.1 The change of gut microbiota before the onset of PD 14 2.2.2 The source of daily microbial oscillation 15 2.2.3 dLAN affects the gut microbiota and the progression of PD 15 2.3 Illumina MiSeq sequencing 16 2.3.1 Total fecal DNA extraction 16 2.3.2 16S metagenomic library preparation 17 2.3.3 Pooling and quality control 20 2.3.4 Next Generation Sequencing (NGS) 20 2.4 Microbiota sequence analysis 20 2.4.1 Sequence assembling and identification 20 2.4.2 Composition analysis 22 2.4.3 Diversity analysis 23 2.4.4 Microbe abundance analysis 23 2.4.5 Circadian analysis of microbial oscillations 24 2.5 Virus injection 24 2.6 Beam balance test 24 2.7 Rotarod test 25 2.8 Immunocytochemistry 26 2.9 Statistical analysis 27 Chapter III Results 28 3.1 PD mice exhibit behavioral motor deficit and reduced TH neuron number around 10.5 months old 28 3.2 Dysbiosis can be observed in young adult PD mice 29 3.3 The daily oscillation of gut microbes is dampened in PD mice 31 3.4 dLAN alters the daily oscillation of gut microbes 32 3.5 Rhythms of gut microbiota oscillation remains robust in Villin-cre cKO mice 34 3.6 Oscillatory rhythm of gut microbes is regulated by light and circadian clock 36 3.7 dLAN accelerates PD progression and advances PD symptoms in brain but not in gut 40 Chapter IV Discussion 43 4.1 Early dysbiosis and dampened gut microbe daily oscillation in animal models of Parkinson's disease 43 4.2 The gut microbiota rhythmicity is controlled by light and the circadian clock 48 4.3 The influence of dLAN on Parkinson’s disease 49 Significance of the Work 51 References 53 Figure 1. Experimental Design of PD gut microbiota longitudinal analysis. 70 Figure 2. Representative mid-brain sections of 2 months old and 10.5 months old SNCA p.A53T and control mice. 71 Figure 3. Results of Beam Balance Test and Rotarod Test of SNCA p.A53T and control mice. 73 Figure 4. Phylum level relative abundance of the gut microbiota and the F/B ratio of SNCA p.A53T and control mice. 75 Figure 5. Composition of the gut microbiota of 2 months old SNCA p.A53T and control mice. 76 Figure 6. Composition of the gut microbiota of 4 months old SNCA p.A53T and control mice. 78 Figure 7. Composition of the gut microbiota of 6.5 months old SNCA p.A53T and control mice. 80 Figure 8. Composition of the gut microbiota of 8.5 months old SNCA p.A53T and control mice. 82 Figure 9. Composition of the gut microbiota of 10.5 months old SNCA p.A53T and control mice. 84 Figure 10. All-age-point pooling PCoA plots of SNCA p.A53T and control mice. 86 Figure 11. Diversity of the gut microbiota of SNCA p.A53T and control mice. 87 Figure 12. Linear discriminant analysis Effect Size (LEfSe) of 2 months old SNCA p.A53T and control mice. 88 Figure 13. Linear discriminant analysis Effect Size (LEfSe) of 4 months old SNCA p.A53T and control mice. 91 Figure 14. Linear discriminant analysis Effect Size (LEfSe) of 6.5 months old SNCA p.A53T and control mice. 93 Figure 15. Linear discriminant analysis Effect Size (LEfSe) of 8.5 months old SNCA p.A53T and control mice. 95 Figure 16. Linear discriminant analysis Effect Size (LEfSe) of 10.5 months old SNCA p.A53T and control mice. 97 Figure 17. Gut microbes’ diurnal oscillatory rhythm of all-age-point SNCA p.A53T and control mice. 98 Figure 18. Experimental Design of WT mice treated with normal light-dark cycle (LD) or dim light at night (dLAN). 100 Figure 19. Composition of the gut microbiota of WT mice treated with normal light-dark cycle (LD) or dim light at night (dLAN). 101 Figure 20. Gut microbiota phylum level relative abundance of mice treated with normal light-dark cycle (LD) or dim light at night (dLAN). 103 Figure 21. Gut microbiota diversity of LD and dLAN mice. 104 Figure 22. Abundance analysis of the gut microbiota of LD and dLAN mice. 106 Figure 23. Gut microbes’ diurnal oscillatory rhythm of LD and dLAN mice. 107 Figure 24. Metabolic status of mice housed under LD and dLAN condition. 108 Figure 25. Representative figures of actogram and the power of the chi-square periodogram of Villin-cre conditional knockout and control mice. 109 Figure 26. Composition of the gut microbiota of Villin-cre conditional knockout and control mice. 110 Figure 27. Gut microbiota phylum level relative abundance of Villin-cre conditional knockout and control mice. 112 Figure 28. Gut microbiota diversity of Villin-cre conditional knockout and control mice. 113 Figure 29. Linear discriminant analysis Effect Size (LEfSe) of Villin-cre conditional knockout and control mice. 114 Figure 30. Gut microbes’ diurnal oscillatory rhythm of Villin-cre conditional knockout and control mice. 116 Figure 31. Metabolic status of Villin-cre conditional knockout and control mice. 118 Figure 32. Representative figures of actogram and the power of the chi-square periodogram of Nestin-cre conditional knockout and control mice. 119 Figure 33. Composition of the gut microbiota of Nestin-cre conditional knockout and control mice. 121 Figure 34. Gut microbiota phylum level relative abundance of Nestin-cre conditional knockout and control mice. 123 Figure 35. Gut microbiota diversity of Nestin-cre conditional knockout and control mice. 124 Figure 36. Linear discriminant analysis Effect Size (LEfSe) of Nestin-cre conditional knockout and control mice. 126 Figure 37. Gut microbes’ diurnal oscillatory rhythm of Nestin-cre conditional knockout and control mice. 127 Figure 38. Experimental design of SCN lesion knockout mice. 129 Figure 39. Representative figures of actogram and the power of the chi-square periodogram of SCN lesion and control mice in DD and LD condition. 131 Figure 40. Coronal mouse mid-brain sections of SCN lesion and control mice. 132 Figure 41. Composition of the gut microbiota of SCN lesion and control mice under LD condition. 133 Figure 42. Composition of the gut microbiota of SCN lesion and control mice under DD condition. 135 Figure 43. Gut microbiota phylum level relative abundance of SCN lesion and control mice. 137 Figure 44. Gut microbiota diversity of SCN lesion and control mice. 138 Figure 45. Linear discriminant analysis Effect Size (LEfSe) of SCN lesion and control mice under LD condition. 140 Figure 46. Linear discriminant analysis Effect Size (LEfSe) of SCN lesion and control mice under DD condition. 142 Figure 47. Gut microbes’ diurnal oscillatory rhythm of SCN lesion and control mice. 143 Figure 48. Vann diagram of oscillating OTUs in control mice under LD or DD condition. 145 Figure 49. Quantification of expression of p-α-synuclein, Occludin, p-LRRK2, LRRK2, NOD2 and p-NF-κB in the colon of SNCA p.A53T and control mice under LD and dLAN conditions. 146 Figure 50. Weighted PCoA plots of SNCA p.A53T and control mice under LD and dLAN conditions from 6.5 months to 10.5 months old. 148 Figure 51. Representative mid-brain sections of 10.5 months old SNCA p.A53T and control mice under LD and dLAN conditions. 150 Figure 52. Results of Beam Balance Test and Rotarod Test of SNCA p.A53T and control mice under dLAN condition from 6.5 months old to 10.5 months old. 152 Table 1. Primers used in metagenomics sample preparation 153 Table 2. Primers of Nextera® Index 154 Appendix I 16S Metagenomic Analysis Pipeline 155 "
dc.language.iso	en
dc.title	帕金森氏症小鼠發病前腸道菌的長期研究	zh_TW
dc.title	The longitudinal analysis of gut microbiota prior to the onset of motor dysfunctions in Parkinson's disease mouse model	en
dc.date.schoolyear	109-2
dc.description.degree	碩士
dc.contributor.oralexamcommittee	林靜嫻(Hsin-Tsai Liu),江皓森(Chih-Yang Tseng),朱家瑩
dc.subject.keyword	腸道菌,生理時鐘,帕金森氏症,	zh_TW
dc.subject.keyword	gut microbiota,circadian rhythm,Parkinson’s disease,	en
dc.relation.page	159
dc.identifier.doi	10.6342/NTU202103215
dc.rights.note	同意授權(全球公開)
dc.date.accepted	2021-09-17
dc.contributor.author-college	生命科學院	zh_TW
dc.contributor.author-dept	生命科學系	zh_TW
顯示於系所單位：	生命科學系

文件中的檔案：

檔案	大小	格式
U0001-1609202116554500.pdf	13.89 MB	Adobe PDF	檢視/開啟

顯示文件簡單紀錄

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。