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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王培育(Pei-Yu Wang) | |
| dc.contributor.author | I-Ya Lin | en |
| dc.contributor.author | 林儀雅 | zh_TW |
| dc.date.accessioned | 2021-06-17T09:06:33Z | - |
| dc.date.available | 2025-03-13 | |
| dc.date.copyright | 2020-03-13 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-12-31 | |
| dc.identifier.citation | Anson, R. M., Guo, Z., de Cabo, R., Iyun, T., Rios, M., Hagepanos, A., . . . Mattson, M. P. (2003). Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A, 100(10), 6216-6220. doi:10.1073/pnas.1035720100
Anton, S., & Leeuwenburgh, C. (2013). Fasting or caloric restriction for healthy aging. Exp Gerontol, 48(10), 1003-1005. doi:10.1016/j.exger.2013.04.011 Antunes, M., & Biala, G. (2012). The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process, 13(2), 93-110. doi:10.1007/s10339-011-0430-z Bali, A., & Singh, S. (2015). Serotonergic 5-HT6 Receptor Antagonists: Heterocyclic Chemistry and Potential Therapeutic Significance. Curr Top Med Chem, 15(17), 1643-1662. Barnes, N. M., & Sharp, T. (1999). A review of central 5-HT receptors and their function. Neuropharmacology, 38(8), 1083-1152. Benhamu, B., Martin-Fontecha, M., Vazquez-Villa, H., Pardo, L., & Lopez-Rodriguez, M. L. (2014). Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in Alzheimer's disease. J Med Chem, 57(17), 7160-7181. doi:10.1021/jm5003952 Bentley, R. A., Ross, C. N., & O'Brien, M. J. (2018). Obesity, Metabolism, and Aging: A Multiscalar Approach. Prog Mol Biol Transl Sci, 155, 25-42. doi:10.1016/bs.pmbts.2017.11.016 Bevins, R. A., & Besheer, J. (2006). Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory'. Nat Protoc, 1(3), 1306-1311. doi:10.1038/nprot.2006.205 Braeckman, B. P., Demetrius, L., & Vanfleteren, J. R. (2006). The dietary restriction effect in C. elegans and humans: is the worm a one-millimeter human? Biogerontology, 7(3), 127-133. doi:10.1007/s10522-006-9003-4 Burger, J. M., Buechel, S. D., & Kawecki, T. J. (2010). Dietary restriction affects lifespan but not cognitive aging in Drosophila melanogaster. Aging Cell, 9(3), 327-335. doi:10.1111/j.1474-9726.2010.00560.x Can, A., Dao, D. T., Terrillion, C. E., Piantadosi, S. C., Bhat, S., & Gould, T. D. (2012). The tail suspension test. J Vis Exp(59), e3769. doi:10.3791/3769 Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., . . . Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201-204. doi:10.1126/science.1173635 Colman, R. J., Beasley, T. M., Kemnitz, J. W., Johnson, S. C., Weindruch, R., & Anderson, R. M. (2014). Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun, 5, 3557. doi:10.1038/ncomms4557 Coppen, A. J. T. B. J. o. P. (1967). The biochemistry of affective disorders. 113(504), 1237-1264. Deacon, R. M. (2013). Measuring motor coordination in mice. J Vis Exp(75), e2609. doi:10.3791/2609 Detke, M. J., Rickels, M., & Lucki, I. (1995). Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology (Berl), 121(1), 66-72. Duan, W., & Mattson, M. P. (1999). Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease. J Neurosci Res, 57(2), 195-206. doi:10.1002/(SICI)1097-4547(19990715)57:2<195::AID-JNR5>3.0.CO;2-P Ennaceur, A. (2010). One-trial object recognition in rats and mice: methodological and theoretical issues. Behav Brain Res, 215(2), 244-254. doi:10.1016/j.bbr.2009.12.036 Filip, M., & Bader, M. (2009). Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system. Pharmacol Rep, 61(5), 761-777. Fisas, A., Codony, X., Romero, G., Dordal, A., Giraldo, J., Merce, R., . . . Pauwels, P. J. (2006). Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats. Br J Pharmacol, 148(7), 973-983. doi:10.1038/sj.bjp.0706807 Foley, A. G., Murphy, K. J., Hirst, W. D., Gallagher, H. C., Hagan, J. J., Upton, N., . . . Regan, C. M. (2004). The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats. Neuropsychopharmacology, 29(1), 93-100. doi:10.1038/sj.npp.1300332 Frassetto, A., Zhang, J., Lao, J. Z., White, A., Metzger, J. M., Fong, T. M., & Chen, R. Z. (2008). Reduced sensitivity to diet-induced obesity in mice carrying a mutant 5-HT6 receptor. Brain Res, 1236, 140-144. doi:10.1016/j.brainres.2008.08.012 Frias, M. A., Thoreen, C. C., Jaffe, J. D., Schroder, W., Sculley, T., Carr, S. A., & Sabatini, D. M. (2006). mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol, 16(18), 1865-1870. doi:10.1016/j.cub.2006.08.001 Gershon, M. D., & Tack, J. (2007). The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology, 132(1), 397-414. doi:10.1053/j.gastro.2006.11.002 Grandison, R. C., Piper, M. D., & Partridge, L. (2009). Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature, 462(7276), 1061-1064. doi:10.1038/nature08619 Hall, M. N. (2008). mTOR-what does it do? Transplant Proc, 40(10 Suppl), S5-8. doi:10.1016/j.transproceed.2008.10.009 Hara, K., Maruki, Y., Long, X., Yoshino, K., Oshiro, N., Hidayat, S., . . . Yonezawa, K. (2002). Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell, 110(2), 177-189. doi:10.1016/s0092-8674(02)00833-4 Heal, D., Gosden, J., & Smith, S. (2011). The 5-HT6 receptor as a target for developing novel antiobesity drugs. Int Rev Neurobiol, 96, 73-109. doi:10.1016/B978-0-12-385902-0.00004-8 Heal, D. J., Smith, S. L., Fisas, A., Codony, X., & Buschmann, H. (2008). Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol Ther, 117(2), 207-231. doi:10.1016/j.pharmthera.2007.08.006 Houtkooper, R. H., Williams, R. W., & Auwerx, J. (2010). Metabolic networks of longevity. Cell, 142(1), 9-14. doi:10.1016/j.cell.2010.06.029 Jacinto, E., & Hall, M. N. (2003). Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol, 4(2), 117-126. doi:10.1038/nrm1018 Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Ruegg, M. A., Hall, A., & Hall, M. N. (2004). Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol, 6(11), 1122-1128. doi:10.1038/ncb1183 Johnson, R. K., Appel, L. J., Brands, M., Howard, B. V., Lefevre, M., Lustig, R. H., . . . Prevention. (2009). Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation, 120(11), 1011-1020. doi:10.1161/CIRCULATIONAHA.109.192627 Jura, M., & Kozak, L. P. (2016). Obesity and related consequences to ageing. Age (Dordr), 38(1), 23. doi:10.1007/s11357-016-9884-3 Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005). AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab, 1(1), 15-25. doi:10.1016/j.cmet.2004.12.003 Kaidanovich-Beilin, O., Lipina, T., Vukobradovic, I., Roder, J., & Woodgett, J. R. (2011). Assessment of social interaction behaviors. J Vis Exp(48). doi:10.3791/2473 Kapahi, P., & Zid, B. (2004). TOR pathway: linking nutrient sensing to life span. Sci Aging Knowledge Environ, 2004(36), PE34. doi:10.1126/sageke.2004.36.pe34 Katewa, S. D., & Kapahi, P. (2010). Dietary restriction and aging, 2009. Aging Cell, 9(2), 105-112. doi:10.1111/j.1474-9726.2010.00552.x Kerr, F., Augustin, H., Piper, M. D., Gandy, C., Allen, M. J., Lovestone, S., & Partridge, L. (2011). Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease. Neurobiol Aging, 32(11), 1977-1989. doi:10.1016/j.neurobiolaging.2009.10.015 Khoury, R., Grysman, N., Gold, J., Patel, K., & Grossberg, G. T. (2018). The role of 5 HT6-receptor antagonists in Alzheimer's disease: an update. Expert Opin Investig Drugs, 27(6), 523-533. doi:10.1080/13543784.2018.1483334 Kim, D. H., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument-Bromage, H., . . . Sabatini, D. M. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell, 110(2), 163-175. doi:10.1016/s0092-8674(02)00808-5 Kleiber, M. (1947). Body size and metabolic rate. Physiol Rev, 27(4), 511-541. doi:10.1152/physrev.1947.27.4.511 Kolovou, G. D., Anagnostopoulou, K. K., & Cokkinos, D. V. (2005). Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgrad Med J, 81(956), 358-366. doi:10.1136/pgmj.2004.025601 Kotanska, M., Lustyk, K., Bucki, A., Marcinkowska, M., Sniecikowska, J., & Kolaczkowski, M. (2018). Idalopirdine, a selective 5-HT6 receptor antagonist, reduces food intake and body weight in a model of excessive eating. Metab Brain Dis, 33(3), 733-740. doi:10.1007/s11011-017-0175-1 Kumanyika, S., Jeffery, R. W., Morabia, A., Ritenbaugh, C., Antipatis, V. J., & Public Health Approaches to the Prevention of Obesity Working Group of the International Obesity Task, F. (2002). Obesity prevention: the case for action. Int J Obes Relat Metab Disord, 26(3), 425-436. doi:10.1038/sj.ijo.0801938 Kunz, J., Henriquez, R., Schneider, U., Deuter-Reinhard, M., Movva, N. R., & Hall, M. N. (1993). Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell, 73(3), 585-596. doi:10.1016/0092-8674(93)90144-f Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., . . . Baur, J. A. (2012). Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science, 335(6076), 1638-1643. doi:10.1126/science.1215135 Laplante, M., & Sabatini, D. M. (2012). mTOR signaling in growth control and disease. Cell, 149(2), 274-293. doi:10.1016/j.cell.2012.03.017 Leger, M., Quiedeville, A., Bouet, V., Haelewyn, B., Boulouard, M., Schumann-Bard, P., & Freret, T. (2013). Object recognition test in mice. Nat Protoc, 8(12), 2531-2537. doi:10.1038/nprot.2013.155 Leiter, E. H., Premdas, F., Harrison, D. E., & Lipson, L. G. (1988). Aging and glucose homeostasis in C57BL/6J male mice. FASEB J, 2(12), 2807-2811. doi:10.1096/fasebj.2.12.3044905 Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., . . . Hall, M. N. (2002). Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell, 10(3), 457-468. Mao, Z., & Zhang, W. (2018). Role of mTOR in Glucose and Lipid Metabolism. Int J Mol Sci, 19(7). doi:10.3390/ijms19072043 Meffre, J., Chaumont-Dubel, S., Mannoury la Cour, C., Loiseau, F., Watson, D. J., Dekeyne, A., . . . Marin, P. (2012). 5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia. EMBO Mol Med, 4(10), 1043-1056. doi:10.1002/emmm.201201410 Mitchell, E. S., & Neumaier, J. F. (2005). 5-HT6 receptors: a novel target for cognitive enhancement. Pharmacol Ther, 108(3), 320-333. doi:10.1016/j.pharmthera.2005.05.001 Mokdad, A. H., Bowman, B. A., Ford, E. S., Vinicor, F., Marks, J. S., & Koplan, J. P. (2001). The continuing epidemics of obesity and diabetes in the United States. JAMA, 286(10), 1195-1200. doi:10.1001/jama.286.10.1195 Monsma, F. J., Jr., Shen, Y., Ward, R. P., Hamblin, M. W., & Sibley, D. R. (1993). Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol, 43(3), 320-327. Moy, S. S., Nadler, J. J., Perez, A., Barbaro, R. P., Johns, J. M., Magnuson, T. R., . . . Crawley, J. N. (2004). Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav, 3(5), 287-302. doi:10.1111/j.1601-1848.2004.00076.x Oh, Y. S., Seo, E. H., Lee, Y. S., Cho, S. C., Jung, H. S., Park, S. C., & Jun, H. S. (2016). Increase of Calcium Sensing Receptor Expression Is Related to Compensatory Insulin Secretion during Aging in Mice. PLoS One, 11(7), e0159689. doi:10.1371/journal.pone.0159689 Pi-Sunyer, F. X. (2002). The obesity epidemic: pathophysiology and consequences of obesity. Obes Res, 10 Suppl 2, 97S-104S. doi:10.1038/oby.2002.202 Price, J. C., Khambatta, C. F., Li, K. W., Bruss, M. D., Shankaran, M., Dalidd, M., . . . Hellerstein, M. K. (2012). The effect of long term calorie restriction on in vivo hepatic proteostatis: a novel combination of dynamic and quantitative proteomics. Mol Cell Proteomics, 11(12), 1801-1814. doi:10.1074/mcp.M112.021204 Riera, C. E., & Dillin, A. (2015). Tipping the metabolic scales towards increased longevity in mammals. Nat Cell Biol, 17(3), 196-203. doi:10.1038/ncb3107 Riera, C. E., Tsaousidou, E., Halloran, J., Follett, P., Hahn, O., Pereira, M. M. A., . . . Dillin, A. (2017). The Sense of Smell Impacts Metabolic Health and Obesity. Cell Metab, 26(1), 198-211 e195. doi:10.1016/j.cmet.2017.06.015 Ruat, M., Traiffort, E., Arrang, J. M., Tardivel-Lacombe, J., Diaz, J., Leurs, R., & Schwartz, J. C. (1993). A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation. Biochem Biophys Res Commun, 193(1), 268-276. doi:10.1006/bbrc.1993.1619 Ruetenik, A., & Barrientos, A. (2015). Dietary restriction, mitochondrial function and aging: from yeast to humans. Biochim Biophys Acta, 1847(11), 1434-1447. doi:10.1016/j.bbabio.2015.05.005 Sabatini, D. M. (2006). mTOR and cancer: insights into a complex relationship. Nat Rev Cancer, 6(9), 729-734. doi:10.1038/nrc1974 Salvestrini, V., Sell, C., & Lorenzini, A. (2019). Obesity May Accelerate the Aging Process. Front Endocrinol (Lausanne), 10, 266. doi:10.3389/fendo.2019.00266 Sarbassov, D. D., Ali, S. M., Kim, D. H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., . . . Sabatini, D. M. (2004). Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol, 14(14), 1296-1302. doi:10.1016/j.cub.2004.06.054 Saxton, R. A., & Sabatini, D. M. (2017). mTOR Signaling in Growth, Metabolism, and Disease. Cell, 168(6), 960-976. doi:10.1016/j.cell.2017.02.004 Seibenhener, M. L., & Wooten, M. C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp(96), e52434. doi:10.3791/52434 Selman, C., Tullet, J. M., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., . . . Withers, D. J. (2009). Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 326(5949), 140-144. doi:10.1126/science.1177221 Shiotsuki, H., Yoshimi, K., Shimo, Y., Funayama, M., Takamatsu, Y., Ikeda, K., . . . Hattori, N. (2010). A rotarod test for evaluation of motor skill learning. J Neurosci Methods, 189(2), 180-185. doi:10.1016/j.jneumeth.2010.03.026 Sidhu, K. S. (1992). Basis for body weight exponent (0.75) as a scaling factor in energy metabolism and risk assessment. J Appl Toxicol, 12(5), 309-310. Slattery, D. A., & Cryan, J. F. (2012). Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc, 7(6), 1009-1014. doi:10.1038/nprot.2012.044 Sreekumar, R., Unnikrishnan, J., Fu, A., Nygren, J., Short, K. R., Schimke, J., . . . Nair, K. S. (2002). Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle. Am J Physiol Endocrinol Metab, 283(1), E38-43. doi:10.1152/ajpendo.00387.2001 Stanford, S. C. (2007). The Open Field Test: reinventing the wheel. J Psychopharmacol, 21(2), 134-135. doi:10.1177/0269881107073199 Steru, L., Chermat, R., Thierry, B., & Simon, P. (1985). The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl), 85(3), 367-370. Teng, L. L., Lu, G. L., Chiou, L. C., Lin, W. S., Cheng, Y. Y., Hsueh, T. E., . . . Wang, P. Y. (2019). Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement. PLoS Biol, 17(3), e2007097. doi:10.1371/journal.pbio.2007097 Thiebaud, N., Johnson, M. C., Butler, J. L., Bell, G. A., Ferguson, K. L., Fadool, A. R., . . . Fadool, D. A. (2014). Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning. J Neurosci, 34(20), 6970-6984. doi:10.1523/JNEUROSCI.3366-13.2014 Vaughan, K. L., & Mattison, J. A. (2016). Obesity and Aging in Humans and Nonhuman Primates: A Mini-Review. Gerontology, 62(6), 611-617. doi:10.1159/000445800 Ward, R. P., Hamblin, M. W., Lachowicz, J. E., Hoffman, B. J., Sibley, D. R., & Dorsa, D. M. (1995). Localization of serotonin subtype 6 receptor messenger RNA in the rat brain by in situ hybridization histochemistry. Neuroscience, 64(4), 1105-1111. Wei, S., Shi, W., Li, M., & Gao, Q. (2014). Calorie restriction down-regulates expression of the iron regulatory hormone hepcidin in normal and D-galactose-induced aging mouse brain. Rejuvenation Res, 17(1), 19-26. doi:10.1089/rej.2013.1450 Weindruch, R., Walford, R. L., Fligiel, S., & Guthrie, D. (1986). The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr, 116(4), 641-654. doi:10.1093/jn/116.4.641 Weir, J. d. V. J. T. J. o. p. (1949). New methods for calculating metabolic rate with special reference to protein metabolism. 109(1-2), 1-9. Woods, S., Clarke, N. N., Layfield, R., & Fone, K. C. (2012). 5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. Br J Pharmacol, 167(2), 436-449. doi:10.1111/j.1476-5381.2012.02022.x Woolley, M. L., Marsden, C. A., & Fone, K. C. (2004). 5-ht6 receptors. Curr Drug Targets CNS Neurol Disord, 3(1), 59-79. Yang, M., & Crawley, J. N. (2009). Simple behavioral assessment of mouse olfaction. Curr Protoc Neurosci, Chapter 8, Unit 8 24. doi:10.1002/0471142301.ns0824s48 Yang, M., Silverman, J. L., & Crawley, J. N. (2011). Automated three-chambered social approach task for mice. Curr Protoc Neurosci, Chapter 8, Unit 8 26. doi:10.1002/0471142301.ns0826s56 Zhu, H., Guo, Q., & Mattson, M. P. (1999). Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation. Brain Res, 842(1), 224-229. doi:10.1016/s0006-8993(99)01827-2 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74725 | - |
| dc.description.abstract | 飲食節制 (Dietary restriction) 在老化過程中扮演重要角色，許多實驗結果都證明了小鼠能夠透過飲食節制達到增強記憶以及延長壽命的效果。我們的實驗指出，補充人體所需必須胺基酸之一的色胺酸 (tryptophan) 會藉由通過血清素第六型受體 (serotonin receptor 6, HTR6) 進而消除飲食節制造成的記憶增強效果，以上
數據顯示 HTR6 的缺乏會誘導神經狀態改變並與飲食節制的結果相似。 本研究欲探討 HTR6 在老化過程中的作用，將以小鼠作為模式生物進行一系列的行為與代謝分析。我們發現在年輕小鼠上剔除 HTR6 基因並不影響體重、飲食和飲水量，而在肥胖小鼠和老年小鼠則會使體重下降。另外，與飲食節制小鼠相同的結果是，三組 HTR6 基因剔除小鼠均有記憶增強的效果，但並不影響運動、嗅覺以及其他認知功能。其他研究也發現 HTR6 基因剔除小鼠出現代謝上的改變；然而，海馬迴中被 HTR6 所調控之控管營養代謝的訊號分子－mammalian target of rapamycin complex 1 (mTORC1) 在周圍組織中並沒有受到 HTR6 基因剔除的影響。 為了進一步研究 HTR6 對壽命的潛在影響，我們使用生命週期較短的果蠅作為模式生物，並使用 GeneSwitch-Gal4 系統研究過度表達 HTR6 對於壽命的影響。實驗結果顯示過度表達 HTR6 會造成 TOR 訊號的增強，進而誘導果蠅壽命縮短。我們同時也觀察過度表達 HTR6 的果蠅的生理狀態，發現運動活性和耐飢餓能力皆顯著降低。此外，過度表達 HTR6 不會影響其他生理狀態，如食物的攝取、體重和繁殖力。 綜上所述，我們的結果證實剔除 HTR6 可延緩小鼠老化。相反的，過度表達HTR6 則會加速果蠅的老化。 | zh_TW |
| dc.description.abstract | Dietary restriction (DR) plays an important role in aging process and has been shown to induce memory enhancement and extend lifespan in mice. Our previous results showed that a single amino acid tryptophan, supplementation reverses the DR effects of memory enhancement through 5-hydroxytyptamine receptor 6 (HTR6). These findings suggested that HTR6 deficiency might induce a neurological state that mimics DR.
In this study, we aim to investigate the role of HTR6 during the aging process. Several experimental approaches including behavioral tests and metabolic profiles of wild-type and HTR6 knockout mice were examined. There was no difference in body weight, food and water intake in young mice, whereas reduced body weight was observed in the obese HTR6 KO mice and aged HTR6 KO mice without the alteration of food and water intake. Similar to the DR mice, HTR6 KO mice showed enhanced memory performance independent of age and diet, but we did not observe significant difference in motor, olfactory and other connective functions. In addition, we found altered metabolism in HTR6 KO mice, but HTR6 did not affect mTORC1 signaling in peripheral tissues. To further investigate the potential impact of HTR6 on lifespan, we used Drosophila to investigate the effect of HTR6 overexpression using GeneSwitch-Gal4 system (GS system). We observed shortened lifespan upon HTR6 overexpression in flies which were induced by TOR pathway. We observed reduced locomotor activity and reduced resistance to starvation in HTR6 overexpression flies. We observed no difference in food intake, body weight and fecundity between the control and HTR6 overexpression flies. In conclusion, our results suggest that loss of HTR6 prevents aging in mice. In contrast, overexpression of HTR6 accelerated aging by TOR pathway in flies. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T09:06:33Z (GMT). No. of bitstreams: 1 ntu-108-R06454003-1.pdf: 4752803 bytes, checksum: d1211e608147fdb2b8112eaacb91bf7d (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii Abstract iii Abbreviations iv Contents v Chapter 1 Introduction 1 1.1 The benefits of dietary restriction and the underlying mechanisms 1 1.2 Obesity accelerates the aging process 2 1.3 5-hydroxytyptamine receptor 6 (HTR6) 3 1.4 The relation between HTR6 and aging 4 Chapter 2 Materials and Methods 5 2.1 Animals 5 2.2 Behavioral tests 5 2.2.1 Open Field Test 5 2.2.2 Novel Object Recognition Test 6 2.2.3 Three-Chamber Social Test 6 2.2.4 Buried food test 7 2.2.5 Rotarod test 7 2.2.6 Tail suspension test 8 2.2.7 Forced swim test 8 2.3 Metabolic measurement 8 2.4 Glucose and insulin tolerance test 9 2.5 Fly stock 9 2.6 RU486 (Mifepristone) induction 10 2.7 Lifespan assays 10 2.8 Physiological measurements 10 2.8.1 Body weight and feeding assays 10 2.8.2 Fecundity assays 10 2.8.3 Locomotor activity 11 2.8.4 Starvation assays 11 2.9 Immunoblotting 11 2.10 Antibodies 12 2.11 RNA extraction and quantitative real-time PCR 12 2.12 Statistical analysis 13 Chapter 3 Results 14 3.1 HTR6 KO reduced body weight without the alteration of food and water intake in obese mice and aged mice 14 3.2 HTR6 KO mice have better memory performance 14 3.3 HTR6 KO does not impair motor, olfactory and other cognitive functions 15 3.4 The alterations of metabolism in HTR6 KO mice 15 3.5 HTR6 KO does not alter the expression of mTOR downstream signaling in peripheral tissues 17 3.6 HTR6 overexpression induced shorten lifespan in Drosophila melanogaster 17 3.7 HTR6 overexpression reduced locomotor activity and significantly less resistant to starvation in flies 18 Chapter 4 Discussion 19 Chapter 5 Figures 22 Chapter 6 References 39 | |
| dc.language.iso | zh-TW | |
| dc.title | 血清素受體 HTR6 在老化過程中的角色 | zh_TW |
| dc.title | The role of serotonin receptor HTR6 in aging | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 范守仁(Shou-Zen Fan),汪宏達(Horng-Dar Wang) | |
| dc.subject.keyword | 老化,記憶,代謝,血清素受體, | zh_TW |
| dc.subject.keyword | aging,memory,metabolism,serotonin receptor, | en |
| dc.relation.page | 44 | |
| dc.identifier.doi | 10.6342/NTU201902650 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-01-02 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
| 顯示於系所單位： | 腦與心智科學研究所 | |
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