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標題: | 脫附型電噴灑游離法質譜成像探討多系統萎縮症患者腦區的脂質混亂及其與 α- 突觸核蛋白聚集的空間關聯研究 Exploring Lipid Disturbances and its Spatial Association with α-Synuclein Aggregation in MSA Patient Brain Regions via Desorption Electrospray Ionization Mass Spectrometry Imaging |
作者: | 張景曜 Ching-Yao Chang |
指導教授: | 曾宇鳳 Yufeng Jane Tseng |
關鍵字: | 脫附型電噴灑游離法質譜成像,脂質混亂,分子分佈,α-突觸核蛋白,多系統萎縮症, Desorption electrospray ionization mass spectrometry imaging (DESI- MSI),lipid disturbances,molecular distribution,α-synuclein,multiple system atrophy, |
出版年 : | 2023 |
學位: | 碩士 |
摘要: | 多系統萎縮症是一種罕見的神經退化疾病,因伴隨著α-突觸核蛋白的異常堆積而被歸類為一種共核蛋白病。過去有許多研究觀察到多系統萎縮症病人血漿及腦脊髓液中的代謝體變化,但因α-突觸核蛋白堆積導致的代謝體分佈異常仍不清楚。
脫附型電噴灑游離法質譜成像利用軟性離子化技術,幫助辨識並呈現出組織上的分子分佈。我們將脫附型電噴灑游離法質譜成像應用在12個受到多系統萎縮症影響的腦區,包含了前額葉皮質、眶額葉皮質、運動皮質、感覺皮質、枕葉皮質、胼胝體、鉤束、視丘、殼核、尾狀核、小腦蚓部、大腦小腦(小腦外側),比較疾 病與正常組織的脂質表現及其空間分佈。另外,我們利用免疫組織染色法得到α-突觸核蛋白堆積之分佈,將質譜影像及組織染色影像進行空間對準來觀察蛋白質堆積及脂質分佈的空間關聯性。 本研究證實了脫附型電噴灑游離法質譜成像應用於多系統萎縮症相關脂質混亂的可應用性,簡化樣本製備程序並且減少游離法對於組織的傷害。我們也發現多系統萎縮症對於不同腦區造成的脂質混亂以及α-突觸核蛋白與這些脂質分子分佈的空間關聯。 Multiple system atrophy (MSA) is a rare neurodegenerative disease categorized as a synucleinopathy characterized by the abnormal accumulation of α-synuclein. Metabolite changes have been observed in MSA patients' biofluids, such as plasma and cerebrospinal fluid. However, understanding the spatial distribution of these metabolites in different brain regions is still limited. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is a soft ionization technique that can identify and visualize the distribution of molecules in tissues. Here, we applied DESI-MSI to 12 different regions of human brain tissues, including the prefrontal cortex, orbitofrontal cortex, motor cortex, sensory cortex, occipital cortex, corpus callosum, uncinate fascicle, thalamus, putamen, caudate, vermis, and cerebrocerebellum, thus covering most of the affected brain regions in MSA patients. We compared the lipid expression of fresh frozen samples and investigated the distribution of the altered lipids. Additionally, we used immunohistochemistry (IHC) staining to visualize the spatial distribution of α-synuclein. We performed image registration of histological images and mass spectrometry images to explore the correlation between the distribution of α-synuclein and the identified lipids. Our findings demonstrated the utility of DESI-MSI in analyzing MSA-related lipid disturbances in brain tissues with a simple sample preparation process and minimal tissue damage. Moreover, our study provides insight into the spatial distribution of lipids in different brain regions affected by MSA and their correlation with the distribution of α- synuclein. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91207 |
DOI: | 10.6342/NTU202304442 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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