沈哲鯤臺灣大學：分子醫學研究所李佩芝Lee, Pei-ChihPei-ChihLee2007-11-262018-07-092007-11-262018-07-092004http://ntur.lib.ntu.edu.tw//handle/246246/51386大腦在演化、遺傳、發育、經驗或疾病等因子的交互影響下，而產生了左右腦的不對稱。先前的研究結果顯示大腦在形態、弁鄐峇壑l等層面皆有左右不對稱的情形，此左右腦之不對稱已知與釵h神經性疾病相關。我們利用微陣列生物晶片雜合實驗以及二維膠體電泳技術，大規模搜尋在小鼠腦部不對稱表現之基因，並藉此發現了數個在左右腦海馬迴的部份表現不對稱的基因。進一步的研究顯示，其中一個名為Transthyretin (簡稱Ttr) 的基因在雄性小鼠的左右腦室有明顯的左右不對稱之表現。Ttr在腦部主要是由脈絡叢細胞所合成，我們發現Ttr在腦部左右不對稱的表現極可能源於左右腦室中脈絡叢的分布不均。相對於在雄鼠中顯著的不對稱情形，Ttr在多數的雌性小鼠左右腦室的分布則較為對稱，顯示Ttr左右腦不對稱表現的現象與性別相關。目前已知Ttr的弁鄍D要在於甲狀腺素及維生素Ａ的運送，此外，近來的研究指出Ttr可以隔離可溶性的β-amyloid，進而阻止其聚集以預防阿茲海默症的發生。根據先前的文獻以及我們在實驗上的發現，我們猜測Ttr在左右腦不對稱之表現可能與阿茲海默症有關，此一論點有待更深入的研究加此証明。Brain asymmetry is thought to reflect evolutionary, genetical, developmental, experiential and pathological factors. Accumulating evidence suggests that the brain is asymmetrical in anatomical, functional and neurochemical aspects, and such asymmetry has been linked with several neurological diseases. With the use of gene profiling by microarray hybridization and two-dimension electrophoresis, we performed a global search for asymmetrically expressed genes in the mouse brain. Several candidate genes were found to be expressed asymmetrically within the left and right hippocampus. The transcript of one of these genes, Transthyretin (Ttr), exhibited sex-dependent asymmetry of distribution between the left and right ventricles in the male mice. This asymmetry appeared to be the result of uneven distribution of the choroid plexus cells, in which Ttr is synthesized within the brain. In most females, however, Ttr expression was more symmetrical in the lateral ventricles. In view of the known functions of Ttr in the transport of thyroid hormone and vitamin A, and its capacity of the sequestration of soluble β-amyloid, we speculate on a relationship between Ttr asymmetry and Alzheimer’s disease.Abstract 1 中文摘要 2 Introduction 3 Categorization of brain asymmetry 3 Temporal lobe and hippocampus asymmetries 6 Advantages, development and characters of brain asymmetry 7 Asymmetry-related diseases 8 Gender and asymmetry 9 Evolution of brain asymmetry 9 Global screen for molecular brain asymmetry 11 Materials and Methods 13 Results 20 Asymmetrical gene expression from microarray analysis 20 Randomization of asymmetrically expressed genes 21 Detection of candidate genes mRNA distribution by in situ hybridization 22 Asymmetrical expression of Ttr correlated to choroid plexus cell distribution...23 Asymmetrical protein expression by 2D electrophoresis 24 Discussion 26 The use of microarray technology for brain asymmetry research 26 Ttr is an asymmetrically expressed gene in rodent brain 27 Candidate genes from microarray analysis 31 Global search by 2D electrophoresis 34 Limitations of microarray and 2D electrophoresis 34 References 36 Tables and Figures 42776876 bytesapplication/pdfen-US不對稱asymmetryTtrotherhttp://ntur.lib.ntu.edu.tw/bitstream/246246/51386/1/ntu-93-R91448003-1.pdf