酒精對神經幹細胞分化之影響

神經幹細胞是一群具有自我更新及多向分化能力的未成熟細胞。在哺乳類動物的腦中，神經幹細胞在胚胎晚期可以產生出大多數的神經元。近年來的研究報告顯示出神經幹細胞的損傷可能與生理上以及精神疾病有相關聯性，包括了酒癮。因此，本論文主要目的是要探討酒精對神經幹細胞分化的影響及其機制。從14天大的老鼠胚胎獲得的神經幹細胞以神經球的形式增殖，在有無dbcAMP促進其分化以及不同濃度的酒精 (50–150 mM) 處理下進行培養，在150 mM 的酒精處理下會造成些微神經幹細胞死亡的現象，而50 mM 以及100 mM 的酒精處理下會減少神經幹細胞的分化，但對於神經幹細胞的存活度並無影響。西方墨點法顯示酒精會抑制 ERK 以及 Tuj–1 的表現量，更進一步由型態上的觀察證明了酒精會影響神經突起的生長。先前的研究結果證明 dbcAMP 會經由 ERK 的訊息傳遞路徑誘導神經幹細胞分化作用。基於這些實驗結果，我們推論酒精破壞神經幹細胞分化作用是經由 ERK 的訊息路徑。由結果可推測，酒精對於神經網絡上的損傷可能是藉由減少神經突長，這可用來解釋一些常見的有關於大腦功能異常的疾病例如胎兒酒精症候群。

關鍵字

分化；神經突長；神經幹細胞；酒精；胎兒酒精症候群

並列摘要

Neural stem cells (NSCs) defined as immature cells with self–renewing and multipotent abilities. In the mammalian brain, most neurons are generated by NSCs in the later embryonic period. Recent studies have described the possible relevance of impaired NSCs’ functions to the pathophysiology of psychiatric disorders, including alcoholism. Therefore, the aim of the present study was to investigate the effects and mechanism of ethanol on the differentiation of NSCs. NSCs obtained from 14–day–old rat embryos were propagated as neurospheres and cultured under differential conditions with or without dbcAMP and various concentrations of ethanol（50–150 mM）. Ethanol exposure slightingly increased NSCs death at 150 mM, while 50 to 100 mM ethanol reduced neuronal differentiation without affecting the viability of NSCs. Western blot analysis revealed that ethanol suppressed phosphorylation of extracellular signal–regulated kinase（ERK）and Tuj–1 expression. Furthermore, morphological observation demonstrated that ethanol reduced neurite outgrowth. Previous studies showed that dbcAMP–induced neural differentiation required ERK signaling. Based on these results, we postulate that ethanol disrupts neural differentiation via ERK–dependent pathway. It is possible that ethanol exposure impaired neural network by reducing neurite outgrowth, which may contribute to an explanation of the defects in brain function often observed in fetal alcohol syndrome.

並列關鍵字

neural stem cell ； ethanol ； neurite outgrowth ； fetal alcohol syndrome ； differentiation

參考文獻

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酒精對神經幹細胞分化之影響

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