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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 江皓森 | zh_TW |
| dc.contributor.advisor | Hao-Sen Chiang | en |
| dc.contributor.author | 陳沐柔 | zh_TW |
| dc.contributor.author | Mu-Jou Chen | en |
| dc.date.accessioned | 2025-09-17T16:29:04Z | - |
| dc.date.available | 2025-09-18 | - |
| dc.date.copyright | 2025-09-17 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-06 | - |
| dc.identifier.citation | 1. Poewe, W., et al., Parkinson disease. Nature Reviews Disease Primers, 2017. 3(1): p. 17013.
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Fisher, Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism. Free Radical Biology and Medicine, 2005. 38(11): p. 1422–1432. 70. Turnbull, S., et al., α-synuclein implicated in Parkinson’s disease catalyses the formation of hydrogen peroxide in vitro. Free Radical Biology and Medicine, 2001. 30(10): p. 1163–1170. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99722 | - |
| dc.description.abstract | 帕金森氏症是一種神經退化性疾病，患者腦部的多巴胺神經中會有大量α-突觸核蛋白的堆積。雖然有越來越多證據顯示腸道免疫與帕金森氏症有著緊密關係，但腸道免疫細胞是否會影響α-突觸核蛋白在腸道神經內的堆積仍然未知。我的研究目的是想知道α-突觸核蛋白會如何影響腸道內的免疫狀況，以及免疫細胞是否也能反過來影響α-突觸核蛋白的堆積。利用過度表現人類α-突觸核蛋白的 A53T 轉基因小鼠 (lineG2-3, JXA:006823)，我分離其富有神經本體的腸道肌肉層，並利用免疫螢光染色或流式細胞術檢視其中的免疫細胞族群。我發現A53T轉基因小鼠腸道肌肉層中的 T細胞，巨噬細胞，B細胞，以及巨噬細胞趨化因子Ccl6與過氧化物酶Prdx6b的基因表現與野生型小鼠有所不同。為了知道免疫細胞是否會影響腸道神經內α-突觸核蛋白的堆積，我也透過共培養腸道神經與CD4+ T細胞，初步發現他們會導致α-突觸核蛋白在腸道神經中的總量稍微上升。總而言之，這些結果都顯示α-突觸核蛋白與腸道神經附近的免疫細胞有著雙向的影響。 | zh_TW |
| dc.description.abstract | Parkinson’s disease (PD) is a neurodegenerative disease characterized by the aggregation of protein alpha-synuclein in dopaminergic neurons in the brain. While the connection of PD with gut immune condition is becoming increasingly evident, it is still unknown whether immune cells in the gut can affect alpha-synuclein aggregation in the enteric neurons. Our research aim is to examine whether alpha-synuclein can affect gut immune status and whether immune cells can, in turn, influence alpha-synuclein accumulation. Using human alpha-synuclein overexpressed A53T transgenic mice (lineG2-3, JXA:00682) as an animal model for PD, I isolated the muscularis layer rich in enteric neural bodies from the mice colon and examined the immune cell population using IF staining or flow cytometry. We found the composition of T cells, macrophages, B cells, as well as the expression of macrophage chemokine Ccl6 and anti-oxidant enzyme Prdx6b, was different in the A53T colon muscularis layer compared to wild-type mice. Also, to investigate whether immune cells can influence alpha-synuclein aggregation in the enteric neurons, I co-cultured CD4+ T cells with primary enteric neurons. Preliminary results showed that CD4+ T cells caused a slight increase in the amount of alpha-synuclein in the enteric neurons. These results demonstrated a two-way influence of alpha-synuclein and immune cells near the enteric neurons. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-17T16:29:04Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-17T16:29:04Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 ................................................................................................................................... i
中文摘要 .......................................................................................................................... ii Abstract ............................................................................................................................ iii Contents ........................................................................................................................... iv Chapter 1 Introduction ...................................................................................................... 1 1.1 Parkinson’s disease (PD) .................................................................................. 1 1.1.1 PD symptoms and pathogenesis ............................................................... 1 1.1.2 PD and the gastrointestinal tract ............................................................... 2 1.1.3 Gut-first PD pathogenesis ......................................................................... 3 1.2 Alpha-synuclein (α-synuclein) ......................................................................... 4 1.2.1 Structure and physiological function ........................................................ 4 1.2.2 Pathological α-synuclein .......................................................................... 6 1.2.3 α-synuclein mutations and PD .................................................................. 7 1.2.4 α-synuclein and the immune system ......................................................... 9 1.3 The enteric nervous system (ENS) ................................................................. 10 1.3.1 Enteric neuron function and categories .................................................. 10 1.3.2 The role of α-synuclein in the ENS ........................................................ 12 1.3.3 ENS-immune cells interaction ................................................................ 12 1.4 Rationale and specific aim .............................................................................. 13 Chapter 2 Materials and Methods ................................................................................... 15 2.1 Mice .................................................................................................................... 15 2.2 Genotyping of the α-synuclein A53T transgenic mice ....................................... 16 2.3 Rotarod performance test .................................................................................... 16 2.4 Open field test ..................................................................................................... 17 2.5 Quantitative PCR ................................................................................................ 17 2.6 Isolation of colon muscularis layer ..................................................................... 17 2.7 Whole-mount immunofluorescence staining of the colon muscularis layer ....... 18 2.8 Immunofluorescence staining of paraffin-embedded slides ............................... 19 2.9 Isolation of immune cells from the colon muscularis layer ................................ 20 2.10 Flow cytometry analysis of immune cells from the colon muscularis layer ..... 21 2.11 Primary ENS culture ......................................................................................... 22 2.12 Immunofluorescence staining of primary ENS culture .................................... 24 2.13 Western blot ...................................................................................................... 24 2.14 Sorting and activation of CD4+ T cells ............................................................. 25 2.15 Co-culture of primary ENS and CD4+ T cells .................................................. 26 2.16 Culture of bone marrow derived macrophages (BMDMs) ............................... 27 Chapter 3. Results ........................................................................................................... 28 3.1 Motor abilities in A53T mice were comparable to wild-type mice prior to four months of age. ...........................28 3.2 A53T mice exhibited increased colonic α-synuclein co-localized with neural fiber compared to wild-type as early as two months of age. ............................... 28 3.3 At 2 months of age, A53T mice exhibited a higher percentage of macrophages and fewer B cells in the colon muscularis layer. At 4 months, the percentage of CD4+ and CD8+ T cells was increased. ................. 30 3.4 A53T mice expressed higher levels of Prdx6b and Ccl6 in their colon muscularis layer. ................................................ 31 3.5 Co-culture of primary enteric neurons with CD4+ T cells for 24 hours induced a slight increase in the amount of α-synuclein monomer in the enteric neurons. ........ 32 3.6 Several immune cells also express α-synuclein. ................................. 33 Figures ................................................... 34 Figure 1. Motor abilities in A53T mice were comparable to wild-type prior to four months of age. ............................... 35 ............................................................ 36 ............................................................ 38 Figure 2. A53T mice exhibited increased colonic α-synuclein colocalized with neural fiber compared to wild type as early as two months of age. .................... 40 Figure 3. The immune cell population in the colon muscularis of A53T mice differs from that of wild-type mice. .............................................................. 46 Figure 4. A53T mice expressed higher levels of Prdx6b and Ccl6 in their colon muscularis layer. ............................................................................ 49 Figure 5. Co-culture of primary enteric neurons with CD4+ T cells for 24 hours induced a slight increase in the amount of α-synuclein monomer in the enteric neurons. ................... 52 Figure 6. α-synuclein expression in the immune cells of A53T mice. ................ 54 Chapter 4. Discussion .......................................................... 55 Chapter 5. Conclusion ...................................................... 61 Tables .................................................................... 62 Table 1. Primer list ....................................................... 62 References ................................................................. 63 | - |
| dc.language.iso | en | - |
| dc.subject | 帕金森氏症 | zh_TW |
| dc.subject | Parkinson's disease | en |
| dc.title | 探究腸道免疫細胞與帕金森氏症α-突觸核蛋白堆積之間的雙向影響 | zh_TW |
| dc.title | Investigating the two-way influence of gut immune cells and alpha-synuclein accumulation in Parkinson’s disease | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林靜嫻;陳示國 | zh_TW |
| dc.contributor.oralexamcommittee | Chin-Hsien Lin;Shih-Kuo Chen | en |
| dc.subject.keyword | 帕金森氏症, | zh_TW |
| dc.subject.keyword | Parkinson's disease, | en |
| dc.relation.page | 68 | - |
| dc.identifier.doi | 10.6342/NTU202503079 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-08-10 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生命科學系 | - |
| dc.date.embargo-lift | 2030-07-30 | - |
| 顯示於系所單位： | 生命科學系 | |
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