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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳示國(Shih-Kuo Chen) | |
| dc.contributor.author | I-Chi Lee | en |
| dc.contributor.author | 李亦騏 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:45:58Z | - |
| dc.date.available | 2021-07-10T21:45:58Z | - |
| dc.date.copyright | 2020-07-07 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-06-20 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77083 | - |
| dc.description.abstract | 視網膜上的內生感光神經節細胞(ipRGCs)能感知環境的光線，除了能調控哺乳動物的生理時鐘，也影響周邊組織的生理週期並調節多種賀爾蒙的恆定。近期在小鼠模型上的研究顯示，不正常的日夜週期會引起肥胖、胰島素抗性和的腸道菌相的改變，然而目前造成上述結果的生理機制仍大部分未知。實驗室先前的研究顯示，長期夜晚接受微弱光線(dLAN)照射的小鼠腸道菌相組成改變，並使其表現週期紊亂。在此研究中，我們比較飼養在正常光週期(LD)與夜晚接受微弱光線(dLAN)照射兩週的小鼠其小腸基因表現，並探討哪些基因的表現受到環境光線影響，進而影響其代謝機制和腸道菌相間的交互關係。研究結果顯示，夜晚接受微弱光照小鼠的腸道免疫基因和對抗發炎反應的基因表現表現較高，也有許多蛋白質和脂質消化吸收的基因表現偏高，例如MMP10與Iglv3。然而遭受夜晚光照而升高的生理時鐘基因(Bmal)，然而在裡用6-OJDA阻絕交感神經後，遭受夜晚光照小鼠的Bmal表現量與正常光照週期小鼠的小腸基因表現量相比有顯著上升。總結本篇研究顯示，遭受夜晚光照的小鼠會經由交感神經引發小腸的發炎反應，但腸道生理時鐘的調控不透過交感神經。 | zh_TW |
| dc.description.abstract | Recent studies have shown that intrinsically photosensitive retinal ganglion cells (ipRGCs) in the retina could transmit environmental light information to influence mammalian circadian central clocks at the suprachiasmatic nucleus (SCN) as well as peripheral circadian oscillations and several physiological hormone homeostases. In previous research, disruption of the normal light-dark cycle causes obesity, insulin resistance, and abnormal gut microbiota oscillation in mice. However, how environmental light influences the gut microbiota and host metabolism remains unknown. In this study, we performed a transcriptome analysis of mouse intestine tissue housed under normal light-dark cycle or dim light at night (dLAN) to investigate the genes regulated by environmental light. We observed the up-regulation of genes such as MMP10 and Iglv3, which are involved in immune response and inflammatory under dLAN condition. Besides, the energy balance relative genes such as protein and fats absorption, and circadian related genes such as Nr1d1 and Bmal show higher expression after 2-3 weeks of dLAN treatment. Specifically, Bmal expression is higher in the duodenum under dLAN whether the sympathetic nerve was eliminated or not. Our result suggested that dim light at night induced small intestine inflammation in mice through the sympathetic nervous system. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:45:58Z (GMT). No. of bitstreams: 1 U0001-1806202013225600.pdf: 5969676 bytes, checksum: 58c9fe5ae3df4eab056303dabce0c0b5 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 誌謝 i 摘要 ii Abstract iii Chapter Ⅰ Introduction 1 1.1 Circadian rhythm 1 1.2 Intrinsically photosensitive retinal ganglion cells (ipRGCs) 2 1.3 The effects of abnormal light-dark cycle on physiological function 3 1.4 The function of the ventromedial hypothalamus (VMH) 4 1.5 The relation between light at night and obesity 5 1.6 Gut-brain axis 5 Statement of purpose 7 Chapter Ⅱ Materials and methods 9 2.1 Animals 9 2.2 Experiment design 10 2.3 Metabolism test 11 2.3.1 Glucose tolerance test (GTT) 11 2.3.2 Insulin tolerance test (ITT) 11 2.4 Transcriptome analysis of intestine tissue 12 2.5 Quantitative real-time polymerase chain reaction (qRT-PCR) 12 2.5.1 RNA extraction 13 2.5.2 Reverse transcription of RNA 14 2.6 Immunofluorescence staining 14 2.7 Statistical analysis 15 Chapter Ⅲ Results 16 3.1 Dim light at night (dLAN) condition can increase mice body weight. 16 3.2 Light at night alters gene expressions in the small intestine in two weeks. 17 3.3 The NGS analysis in the ileum under four weeks of light treatment. 19 3.4 Elimination of the sympathetic nerve through 6-OHDA. 21 3.5 Validation of the NGS identified genes in two weeks by qPCR. 22 3.6 Validation of the DEGs in two weeks of light treatment. 23 3.7 The light could activate anterior ventromedial hypothalamus neurons 24 3.8 The light-activated non-SF1 neurons in aVMH. 25 Chapter Ⅳ Discussion 26 4.1 The light at night causes differential expressed genes compared to LD mice. 26 4.2 The dLAN condition increases immune gene related to gut microbiota. 27 4.3 The dLAN condition changed circadian clock genes expression level. 28 4.4 The pathways of dLAN-induced effects change energy homeostasis. 29 4.5 Acute light exposure at night-time activated non-SF1 neurons in aVMH. 30 Significance of the work 31 References 33 Figures. 39 Figure 1. Experiment design. 39 Figure 2. Metabolic status of light-treated male mice in six weeks. 40 Figure 3. Glucose tolerance test in wild-type male mice for six weeks. 41 Figure 4. Metabolic status of light-treated mice for two weeks. 42 Figure 5. Venn diagram of gene expression in LD and dLAN group. 43 Figure 6. Filtering the differential expression genes by NGS analysis (p-adj<0.05). 44 Figure 7. Gene ontology (GO) enrichment bar chart of DEGs 45 Figure 8. Filtering the differential expression genes by NGS analysis. 46 Figure 9. Gene ontology (GO) enrichment bar chart of DEGs. 47 Figure 10. Metabolic status of light-treated mice in 4 weeks for NGS-2 48 Figure 11. Glucose metabolism of wild-type mice treated with light for four weeks. 49 Figure 12. Volcano plot of DEGs distribution and significance in the ileum of mice. 50 Figure 13. Top thirty enrich GO term of up and down-regulated genes. 51 Figure 14. Bodyweight of control and chemical sympathectomy mice. 52 Figure 15. Validation of expression patterns in the ileum of control mice. 53 Figure 16. The RNA expression level of nutrient absorption genes and immune response in the ileum of mice. 54 Figure 17. Verification of nutrient absorption genes in the duodenum of mice. 55 Figure 18. The RNA expression level of Mmp10 in the small intestine. 56 Figure 19. The RNA expression level of Nr1d1 in the small intestine. 57 Figure 20. The RNA expression level of Nfil3 in the small intestine. 58 Figure 21. The RNA expression level of mBmal in the small intestine. 59 Figure 22. The light-activated neurons presented in the SCN in wildtype mice. 60 Figure 23. The light-activated neurons show in the aVMH in wildtype mice. 61 Figure 24. Quantification of light-activated neurons in the SCN and the aVMH in wildtype mice. 62 Figure 25. The light-activated neurons show in the SCN in SF1-tdtomato mouse. 63 Figure 26. The light-activated neurons show in the aVMH in SF1-tdtomato mouse. 64 Figure 27. The number of activated neurons in SF1-tdtomato mouse in the aVMH. 65 Table 1. List of primer and annealing temperature for genotyping 66 Table 2. Gene Up-regulated after housed under dLAN for two weeks in padj. 67 Table 3. Gene down-regulated after housed under dLAN for two weeks in padj. 68 Table 4. Gene Up-regulated after housed under dLAN for two weeks in pval. 69 Table 5. Gene down-regulated after housed under dLAN for two weeks in pval.. 75 Table 6. Gene up-regulated after housed under dLAN condition for four weeks. 77 Table 7. Gene down-regulated after housed under dLAN condition for four weeks. 78 Appendix Abstract and posters 79 | |
| dc.language.iso | en | |
| dc.subject | 腸道菌 | zh_TW |
| dc.subject | 夜晚接受微弱光線 | zh_TW |
| dc.subject | 交感神經 | zh_TW |
| dc.subject | 生理時鐘 | zh_TW |
| dc.subject | 小腸基因 | zh_TW |
| dc.subject | circadian clock | en |
| dc.subject | dLAN | en |
| dc.subject | sympathetic nervous | en |
| dc.subject | small intestine | en |
| dc.title | 夜晚光照影響腸道的基因表現 | zh_TW |
| dc.title | Exposure to light at night influences intestinal transcriptome pattern | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江皓森(Hao-Sen Chiang),周銘翊(Ming-Yi Chou),楊世斌(Shi-Bing Yang) | |
| dc.subject.keyword | 夜晚接受微弱光線,交感神經,生理時鐘,小腸基因,腸道菌, | zh_TW |
| dc.subject.keyword | dLAN,sympathetic nervous,circadian clock,small intestine, | en |
| dc.relation.page | 82 | |
| dc.identifier.doi | 10.6342/NTU202001038 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-06-22 | |
| 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 | |
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