高血糖症對發育中大腦皮質神經形態及粒腺體活性的影響

高血糖症是糖尿病的主要病理特徵。研究顯示高血糖症除了導致糖尿病及其併發症外，也和老年性白內障、動脈硬化、阿茲海默症、巴金森症、以及肌萎縮性脊髓側索硬化症等神經退化性疾病密切相關。本實驗探討高血糖症對神經型態與粒線體活性的影響，以為日後進一步研究神經退化性疾病尋找線索。此研究主要分二部份。第一部份利用共軛焦顯微鏡三度空間影像來觀察神經突軸及樹突棘的形態及密度。第二部份利用四甲基羅丹明酯的螢光變化以及細胞存活率分析來探討粒線體的活性。我們研究結果顯示高葡萄糖培養下，神經突軸有減少的趨勢，而神經樹突棘的密度增加。另一方面，以四甲基羅丹明酯的螢光變化檢測，結果顯示粒線體膜電位呈現明顯下降。但是，細胞存活率分析的結果卻指出細胞無明顯死亡。此研究結果可用來解釋妊娠糖尿病導致新生兒大腦異常的病因，也可為神經退化性疾病致病機制提供線索。未來研究將規劃對糖尿病母親及其胎兒進行活體研究，並將研究結果與本研究結果進行比較分析，以進一步探索高血糖對粒線體去氧核醣核酸的影響。

關鍵字

高血糖症；糖尿病；老年性白內障；動脈硬化；阿茲海默症；巴金森症；肌萎縮性脊髓側索硬化症；神經退化性疾病；共軛焦顯微鏡；突軸；樹突棘；四甲基羅丹明酯；細胞存活率分析；粒線體；粒線體去氧核醣核酸

並列摘要

Hyperglycemia is a key pathogenetic feature of diabetes mellitus and diabetic complications. There is considerable evidence that hyperglycemia is not only closely related to diseases such as senile cataracts and arteriosclerosis, but is also implicated in neurodegenerative diseases Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). In this study, we are interested in the defects in neuronal morphology and mitochondrial activity caused by high glucose insult as a first step toward understanding the events that underlie the development of neurodegenerative diseases. To characterize the effects of high glucose on neurons, this work is divided into two parts, the first part focuses on the morphology of neural dendrites and spine density on the basis of three dimensional (3D) images from confocal microscope; the second part studies the physiological function of mitochondria using TMRM fluorescence and MTT assay. Our findings show that high glucose is associated with drawback in branching point initiation and dendrite extension; in addition, spine outgrowth is abnormal. Regarding the mitochondria, the membrane potential across the inner membrane is perturbed as in apoptotic stress but no immediate cell death is observed. Taken together, these phenomena may play important roles in the pathogenesis of maternal hyperglycemia-induced CNS malformations. The result may also be the underlying mechanisms that cause certain aged people more vulnerable to inflict neurodegenerative diseases. In the future, in vivo study on STZ-induced diabetic mother and its embryo will be carried out for comparative study, with further investigation on the effects of hyperglycemia upon mitochondrial deoxyribonucleic acid (mtDNA).

並列關鍵字

Hyperglycemia ； diabetes mellitus ； senile cataracts ； arteriosclerosis ； Alzheimer’s disease ； Parkinson’s disease ； amyotrophic lateral sclerosis ； neurodegenerative disease ； confocal microscope ； dendrite ； spine ； TMRM ； MTT assay ； mitochondria ； mitochondrial deoxyribonucleic acid

參考文獻

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高血糖症對發育中大腦皮質神經形態及粒腺體活性的影響

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