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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 | 鐘浩毓 | zh_TW |
| dc.contributor.author | Hao-Yu Chung | en |
| dc.date.accessioned | 2026-03-05T16:34:01Z | - |
| dc.date.available | 2026-03-06 | - |
| dc.date.copyright | 2026-03-05 | - |
| dc.date.issued | 2026 | - |
| dc.date.submitted | 2026-01-30 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101897 | - |
| dc.description.abstract | 腸道中 α-突觸核蛋白（α-synuclein，α-syn）的堆積逐漸被認為是帕金森氏症（Parkinson’s disease, PD）致病過程中的早期事件，且與腸道發炎密切相關，其中發炎會使得嗜中性球在腸道聚集。然而，嗜中性球在腸神經系統（enteric nervous system, ENS）調控中的角色仍未被充分了解。本研究旨在探討嗜中性球是否會影響ENS內α-syn的表現。
為達成此目的，我們自成年小鼠分離含有腸神經元與腸膠細胞的ENS培養系統，並與分離之嗜中性球進行共培養。我們發現，嗜中性球共培養可顯著增加ENS細胞中α-syn的蛋白量，而嗜中性球上清液處理ENS細胞亦呈現相似趨勢，顯示嗜中性球所釋放的可溶性因子可能參與ENS α-syn的調控。此外，嗜中性球共培養導致神經元標記蛋白(marker protein) Tubulin beta-3(TUBB3)及管家蛋白(housekeeping gene) Glyceraldehyde 3-phosphate dehydrogenase(GAPDH)表現下降，並伴隨ENS細胞毒性增加。值得注意的是，嗜中性球共培養抑制了ENS培養中 Snca mRNA 的表現，呈現α-syn蛋白與RNA表現量相反的關係，暗示共培養過程中可能涉及α-syn的轉譯後調控。 綜合上述結果，本研究突顯嗜中性球在調控腸道α-syn表現平衡中的重要角色，並指出嗜中性球驅動的腸道發炎可能參與帕金森氏症腸–腦軸早期致病事件的發生。 | zh_TW |
| dc.description.abstract | Accumulation of α-synuclein (α-syn) in the gastrointestinal tract has been increasingly recognized as an early event in Parkinson’s disease (PD) pathogenesis and is closely associated with intestinal inflammation. During intestinal inflammation, neutrophils are recruited to the gastrointestinal tract. However, the contribution of neutrophils to enteric nervous system regulation remains poorly understood. In this study, we investigated whether neutrophils influence α-syn expression in the enteric nervous system (ENS).
To reach our goal, primary ENS cultures containing enteric neurons and glial cells were isolated from adult mice and co-cultured with isolated neutrophils. We found that neutrophil co-culture significantly increased α-synuclein in ENS cultures with a similar trend observed when ENS cells were incubated with neutrophil-conditioned medium, suggesting that soluble factors released by neutrophils contribute to ENS modulation. This finding suggested soluble factors released by neutrophils contribute to ENS modulation. Neutrophil co-culture also resulted in reduced expression of neuronal markers, TUBB3 and housekeeping proteins, GAPDH and was associated with increased cytotoxicity of ENS cells. Neutrophil co-culture suppressed Snca mRNA expression in ENS cultures, showing an inverse relationship between α-synuclein protein and RNA levels. These results suggest a possible post-translational modification of α-synuclein during the co-culture. Together, our results highlight the role of neutrophils in regulating enteric α-synuclein homeostasis and suggest that neutrophil-driven intestinal inflammation may contribute to early pathogenic events along the gut–brain axis in Parkinson’s disease. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2026-03-05T16:34:01Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2026-03-05T16:34:01Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 ii
中文摘要 iv Abstract vi Contents viii Chapter 1 Introduction 1 1.1.1 Parkinson disease 1 1.1.2 Gut–Brain Axis in Parkinson’s Disease 1 1.1.3 Enteric nervous system in PD: 3 1.1.4 ENS and immune cells 4 1.1.5 alpha-synuclein in gut immune 6 1.1.6 alpha-synuclein post-translational modification 7 1.2.1 Neutrophils 8 1.2.2 Neutrophils and intestinal inflammation 10 1.2.3 Neutrophils and nervous system 10 1.3 Rationale and specific aim 12 Chapter 2 Material & Method 14 2.0 Mice 14 2.1 isolating neutrophil from mice bone marrow 14 2.2 flow cytometry 14 2.3 isolating and culturing enteric neuron and glia cell 15 2.4 neutrophils and ENS cells co-culture 16 2.5 Immunofluorescence staining 17 2.6 Western blot 18 2.7 Gene Expression Analysis 19 2.8 Cytotoxicity test 19 Chapter 3 Results 20 3.1 Neutrophil co-culture increased α-synuclein protein levels in enteric neurons 20 3.2 Neutrophil co-culture reduced neuronal marker expression and increased cytotoxicity in ENS cultures 22 3.3 Neutrophil co-culture suppressed Snca mRNA expression in ENS cultures 23 3.4 Neutrophil-conditioned medium treatment exhibited a trend similar with that observed in direct co-culture 23 Chapter 4 Discussion 25 Chapter 5 Conclusion 30 Figures 31 Fig.1 experiment aim 31 Fig.2 Experimental design 32 Fig 3. Neutrophil co-culture increased α-synuclein protein levels in enteric neurons 35 Fig 4. Neutrophil co-culture showed a trend toward increased cytotoxicity in ENS cultures 36 Fig 5. Neutrophil co-culture showed a trend toward suppressed Snca mRNA expression in ENS cultures 37 Fig 6. Neutrophil-conditioned medium partially recapitulated the effects of direct co-culture 39 Fig.7 conclusion of ENS and neutrophils co-culture 40 References 41 | - |
| dc.language.iso | en | - |
| dc.subject | 嗜中性球 | - |
| dc.subject | α-突觸核蛋白 | - |
| dc.subject | 腸神經系統 | - |
| dc.subject | neutrophil | - |
| dc.subject | alpha-synuclein | - |
| dc.subject | enteric nervous system | - |
| dc.title | 探討嗜中性球對腸神經系統之影響 | zh_TW |
| dc.title | Investigating the effect of neutrophils on the enteric nervous system | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 王偉蓓;陳俊任 | zh_TW |
| dc.contributor.oralexamcommittee | Wei-Bei Wang;Chun-Jen Chen | en |
| dc.subject.keyword | 嗜中性球,α-突觸核蛋白腸神經系統 | zh_TW |
| dc.subject.keyword | neutrophil,alpha-synucleinenteric nervous system | en |
| dc.relation.page | 47 | - |
| dc.identifier.doi | 10.6342/NTU202600381 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2026-02-02 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生命科學系 | - |
| dc.date.embargo-lift | 2026-03-06 | - |
| 顯示於系所單位： | 生命科學系 | |
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