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研究生:洪嬿
研究生(外文):Yen Hung
論文名稱:胎兒酒精症候群引發中樞神經細胞的永久性缺陷
論文名稱(外文):The Permanent Injury of Fetal Alcohol Syndrome (FAS) on Central Neurons
指導教授:陳建榮陳建榮引用關係
指導教授(外文):Jeng-Rung Chen
口試委員:王慈娟陳儷今
口試委員(外文):Yueh-Jan WangLi-Jin Chen
口試日期:2015-06-05
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系暨研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:75
中文關鍵詞:胎兒酒精症候群海馬迴內側嗅皮質錐體細胞神經膠細胞樹突
外文關鍵詞:Fetal Alcohol Syndromehippocampusmedial entorhinal cortexpyramidal neuronsgliadendrite
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胎兒酒精中毒綜合症(Fetal Alcohol Spectrum Disorder, FASD)是母親在懷孕期間飲酒,酒精藉由胎盤進入胎兒體內,影響胎兒的正常發育,進而產下心智與生理缺陷的嬰兒。胎兒酒精中毒綜合症中最嚴重的就是胎兒酒精症候群(Fetal Alcohol Syndrome, FAS),而FAS病患在生長時期會較正常的小孩來得遲緩,具有明顯的臉部特徵之外,也會出現一些神經行為的症狀,像是智能障礙、閱讀書寫障礙、注意力無法集中、感覺綜合失調等。許多研究發現,胎兒時期的酒精暴露會對腦部造成傷害,進而造成中樞神經系統的結構性、神經性及功能性的缺失。而本次研究主要想探討胎兒酒精症候群是否對中樞神經細胞造成細胞型態學的變化,這些變化是否為永久性的。我們利用酒精霧化機以及日常飲水中添加酒精對母鼠從懷孕第一天至出生後30天進行乙醇處理,來誘導嚴重胎兒酒精症候群的大白鼠(FAS rats),而在整個過程會確認大鼠的血液中酒精濃度是否達到250 mg/dl以上。這些老鼠會分別在日齡30天(青春期前)和日齡90天(成年)時進行犧牲,並檢測體重、面部特徵以及腦部大小,結果發現FAS組的老鼠部分臉部特徵出現顯著差異,而體重及腦部出現明顯的生長遲緩現象,其中有部份的臉部特徵、體重及大腦與小腦的大小直至成年都有明顯的差異存在。在行為模式檢測驗評估部份,FAS老鼠在獨木橋試驗中有較差的感覺運動統合協調能力,而水迷宮試驗中也有比較差的學習記憶能力表現。形態學的染色法可見青春期前或成年的FAS老鼠海馬迴CA1以及內側嗅皮質中發現較多的星狀膠細胞、微小膠細胞、 nNOS+,卻有較少的蒲金氏细胞、ChAT+ 纖維、海馬迴CA1及內側嗅皮質錐體細胞的樹突棘密度,胎兒時期的酒精處理是造成神經形態學的變化與功能缺損的主因,同時也會造成胎兒酒精症候群患者終身的心理與生理發育遲緩。

Fetal alcohol spectrum disorders (FASD) is a birth defects that caused by the mother with high levels of alcohol consumption during pregnancy. Fetal alcohol syndrome (FAS) is the most severe form of the FASD. FAS patients display a number of clinical properties, including growth retardation, facial dysmorphology, mental retardation, reading and writing disorders, inability to concentrate, sensory integration disorder. Some studies show that developing neurons can be malformed or have interrupted by prenatal alcohol exposure and this might create structural, neurological or functional defects of central nervous system (CNS). In this study, we explored whether the cellular morphological changes had been induced by FAS and these neuronal changes were permanent or not. We used alcohol atomizer and alcohol liquid diet from the gestation (G1) to postnatal days 30 (P30) to induce serious FAS rats. Their blood alcohol concentrations (BAC) were randomly checked and were all above 250 mg/dl. The rats were sacrified on 30 days old (before puberty) and 90 days old (adult). The body weight, facial dysmorphology (palpebral fissure, philtrum length…) and brain size were measured. Our results showed that most facial dysmorphologies were showed in P30 of ethanol-treated rats (FAS), and growth retardation was found in body weights and brain size. In adult, some facial dysmorphologies, lighter body weight and smaller brain size were still presence. In behavioral tests, FAS rats had poorer performances in spatial learning memory and motor coordination in Morris water maze and beam walking tests respectively. Histologically, the hippocampus and medial entorhinal cortex of FAS rats showed higher density of astrocyte, microglia and nNOS+, but had less purkinje cells in cerebellum, ChAT+ fibers in fimbia of hippocampus, spine density of hippocampal CA1 pyramidal neurons and medial entorhinal cortex pyramidal neurons before puberty and adult. A close relationship between these neuronal changes and functional impairments due to ethanol exposure is strongly suggested, that may be lead to mental and physical retardation associated with FAS patients in lifelong.

中文摘要...................i
Abstract..................ii
目 錄..................iii
前 言..................1
材料與方法.................9
結 果..................21
討 論..................33
結 論..................45
圖表與說明.................46
參考文獻...................67


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