| Abstract: | 慢性睡眠不足或睡眠剝奪為現今工商社會中，廣泛存在影響人類健康的重要問題。睡眠缺乏將導致腦部功能及心理行為發生改變，包括許多重要酵素暨神經傳導物質的減少、神經興奮性(neuronal excitability) 受損或情緒障礙(emotional disturbance) 與認知功能失調(cognitive dysfunction) 的發生。先前的研究已證實，前額葉皮質神經迴路 (prefrontal circuits) 在情緒控制發展與認知功能的調節上，扮演相當重要的角色。藉由廣泛性神經交互投射(reciprocal interconnection) 的運作與諸多神經化學物質與胞內離子的參與，前額葉皮質可直接影響邊緣系統(limbic system)、其他皮質(neocortex) 與皮質下構造(sub-cortical structures) 的活化，進而調控情緒發展與認知功能的運行。隨著工業化社會的到來，睡眠剝奪的現象已逐漸向幼兒及青少年普及，其對日後成年期心智行為與情緒反應的潛在影響，已是不容忽視的重要課題。然而，就我們所知，目前學界對幼年期睡眠剝奪(childhood sleep deprivation) 對日後成年情緒控制發展與認知功能的影響幾無所知；另一方面，幼年期睡眠剝奪對前額葉皮質調控系統，分子與相關神經化學物質活性表現暨功能形態之潛在變化，仍舊付之闕如。緣此，本計畫預計以三年的時間，逐年依次探討(1) 幼年期睡眠剝奪對日後成年期心智運作暨認知行為表現之影響 (2) 結合定量組織化學(histochemistry)、定量免疫組織化學(immunohistochemistry) 與西方墨點反應(Western blotting) 等工具，分別在形態及生化層次上，深入探討心智行為的改變是否與前額葉皮質神經化學物質活性的揚抑有所關連(3) 利用電子顯微鏡 (electron microscopy) 與飛行式二次離子質譜儀(TOF-SIMS) 等貴重儀器，詳細偵測前額葉皮質神經活化的高低是否肇因於離子濃度與超微結構的改變。藉由此計畫的逐年實行，不僅可以提供學界清晰且詳實有關幼年期睡眠剝奪對情緒控制發展與認知功能影響的行為學、神經化學、分子影像學乃至超微結構學證據，同時尚對幼年期睡眠剝奪於破壞心智功能與認知調節的運作上有所了解。我們希望透過此三年期計畫的順利推動與執行，能有效增進學界對前額葉皮質情緒調控機制之認識，同時亦對臨床上宣導幼年期睡眠充足的必要及其作為日後預防或治療心智障礙等相關行為缺失有所幫助與貢獻。
Chronic sleep restriction or sleep deprivation is a common health problem for many people in our current societies. Insufficiency of sleep would cause alterations in brain functions and psychological behaviors including activities of important enzymes, neurotransmitter levels, impaired neuronal excitability, emotional disturbances as well as cognitive dysfunction. Previous studies have indicated that the prefrontal circuits may play an important role in the regulation of emotional control and cognitive modulation. By the broadly presence of reciprocal interconnections, numerous neurochemicals together with intracellular ionic fluctuations, activation of prefrontal cortex would exert its powerful influence on limbic system, other neocortex, and sub-cortical structures, which then regulates the development of emotional control and cognitive activity. With the coming of the industrialization, sleep deprivation has commonly seen in children and adolescence. Examining the potential detrimental effects of childhood sleep deprivation on the development of adult emotional control and cognitive function is thus an important issue in sleep research. However, as we may ascertain, there is a great lack of knowledge regarding the effects of childhood sleep deprivation (CSD) on the development of adult mental disabilities. Moreover, the potential alterations of molecular or neurochemical expressions within the prefrontal cortex following CSD is still remained to be explored. Based on this viewpoint, the present study was designed to examine (1) the potential effects of CSD on adult mental behavior and cognitive changes (2) by the use of quantitative histochemistry, quantitative immunohistochemistry and Western blotting, clearly determine whether the CSD-induced mental dysfunction was attributed to the underlying changes of prefrontal neurochemistry, and (3) with the assistance of electron microscopy and time-of-flight secondary ion mass spectrometry (TOF-SIMS), detailed examine the possible ultrastructural variation and ionic distribution consequently to prefrontal activation changes. By extensively conduct the present study, we can not only provide the detailed behavioral, morphological, molecular and biochemical evidences underlying the detrimental effects of CSD on emotional function, but also greatly increase our knowledge on the mechanisms of CSD related emotional and cognitive disturbances. With the gradually processing of this three-year project, our results will also help us to better recognize the importance of sufficient childhood sleep in emotional development, and offer the possibility for therapeutic strategy in prevention or improving the CSD relevant mental dysfunction persisted to adult stage. |
