DPM 神經元釋放血清素調控果蠅之睡眠行為

DPM neurons release serotonin modulating sleep in Drosophila

陳振欽(Chen-Chin Chen)

指導教授 ： 傅在峰

國立暨南國際大學/科技學院/應用化學系/碩士(2009年)

摘要

睡眠障礙一直是老年人與繁忙都市人口最常見的生理問題。其中包括：失眠、睡眠品質不佳及睡眠週期失序等問題。以果蠅（Fruit fly; Drosophila melanogaster）做為模式動物在睡眠的研究中證實，當果蠅大腦中之神經傳導物質（Neurotransmitter）─血清素（Serotonin; 5-Hydroxytryptamine; 5-HT）增加會促進睡眠的發生，更有研究顯示蕈狀體（Mushroom bodies; MBs）會藉由血清素接受器1A（Serotonin receptor 1A ; d5-HT1A）進而調控果蠅的睡眠行為。近年來，亦有研究指出果蠅腦中的DPM神經元（Dorsal paired medial neuron）所分泌之神經胜肽（Neuropeptide）-Amnesiac（AMN）也負責調控睡眠行為的開始及維持，因DPM神經元將神經纖維深入蕈狀體中，因此也藉由Amnesiac影響蕈狀體對於睡眠行為的調控。利用免疫螢光染色（immune fluorescent staining）的方法，觀察果蠅血清素與相關生合成酵素色胺酸氫化酶（tryptophan hydroxylase; dTRH; TPH2）在果蠅腦中的分布狀況，已有研究初步證實DPM神經元也具有分泌血清素之功能。本研究構築UAS-RNAidTRH基因轉殖果蠅，並藉由DPM神經元表現之C316-GAL4果蠅株，控制UAS-dTRH與UAS-RNAidTRH的表現，進而影響血清素在DPM神經元的生合成。這些操作則顯示，似乎改變血清素在DPM神經元的表現同時都會影響果蠅的睡眠行為。此外，本研究發現所使用之遺傳工具具有洩漏表達現象。針對此問題，建立一套新的誘導系統及低背景的遺傳工具是目前最迫切的。

關鍵字

蕈狀體 ； GAL4/UAS系統 ； Gene-Switch ； RNA干擾 ； 色胺酸氫化酶

並列摘要

The physiological changes associated with aging and pressure are increasing in importance and relevance to the biomedical community as our world’s population ages. Sleep problems and complaints are more common in the aged and urban people, greatly reducing their quality of life. Moreover, this had lead to several fundamental physiological changes in sleep including prolonged sleep-onset time, change in sleep architecture, and increase in awakening from sleep. Recent works have demonstrated the usefulness of the fruit fly Drosophila melanogaster to the study of the fundamental neurobiology of sleep. Latest significant investigation indicated that serotonin can facilitate the sleep of Drosophila, which was related to serotonin receptor 1A (5HT1A) in the mushroom bodies (MBs). We observed a pair of neurons named dorsal paired medial (DPM) neurons amongst those serotonin-positive neurons. Most importantly, the amn gene is demonstrated to be expressed throughout the brain and strongly also in DPM neurons that innervate and modulate the MBs for memory consolidation and responsible to regulate the sleep onset and maintenance. In this study, we find that acute induction of tryptophan hydroxylase (dTRH; TPH2) over expression or knocking down of dTRH by interference RNAi of dTRH in DPM neurons disrupts sleep homeostat. These data seemingly demonstrate the involvement of serotonin in DPM neuron of Drosophila. In addition, the genetic tool used for finding this research has to leak an expression a phenomenon. In view of this question, establishes a set of new inducible system and the low background genetic tool is most urgent at present.

並列關鍵字

mushroom bodies ； GAL4/UAS system ； Gene-Switch ； RNAi ； tryptophan hydroxylase

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