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γ-丁氨基酪酸神經於大鼠內中縫核內調控足電刺激造成之快速動眼期睡眠紊亂

GABAergic Neurons in the Median Raphe Nucleus (MRN) Modulate Footshock-induced Rapid Eye Movement (REM) Sleep Disturbance in Rats

摘要


在受到壓力和焦慮情緒影響下,身體的壓力荷爾蒙或神經傳遞物分泌後造成警覺狀態上升,但也相對造成睡眠上的困擾。Hypocretin(Hcrt)是種腦內促進醒覺的神經傳遞物,同時在壓力的情況下也會大量分泌。分泌的Hcrt廣布到腦中各部位,其中之一的內中縫核(median raphe nucleus, MRN)也是腦中調節睡眠和情緒的腦區。在之前的研究發現,MRN中的抑制性γ-丁氨基酪酸(gamma-aminobutyric acid, GABA)神經元可做為過量分泌Hcrt之調節機制,在功能上也發現GABAA受體拮抗劑(bicuculline)可以增進Hcrt的作用進而抑制壓力所引起的腦波。因此本實驗假設bicuculline也可以抑制壓力引起的睡眠問題。我們利用足電刺激模擬受到壓力刺激的大鼠行為模式,並用微量注射法注射bicuculline或Hcrt至MRN,觀察後續的睡眠狀況。實驗結果顯示bicuculline可以減緩足電刺激所造成的快速動眼(rapid eye movement, REM)睡眠減少,而Hcrt在MRN中所造成的快速動眼睡眠抑制也會受到bicuculline的作用而減緩。實驗結果顯示bicuculline可能藉由抑制Hcrt在MRN的機制使焦慮的症狀緩解,其中包括快速動眼睡眠的減少。

並列摘要


Under stress and/or anxiety, significant amounts of stress hormones and neurotransmitters are released and result in hyperarousal and sleep disturbance. Hypocretin (Hcrt) mediates stress responses in addition to its maintenance of wakefulness. Hcrt is widely distributed in the brain areas, including the median raphe nucleus (MRN), which regulate both sleep and emotion. The GABAergic neurons in the MRN suppress the overactive Hcrt. Our previous study has shown that the GABAA receptor antagonist: bicuculline enhances the effect of Hcrt in the MRN. We herein hypothesized that bicuculline in the MRN influences stress-induced sleep disruptions. Stress was induced by electrical footshock and microinjected the pharmacological blockade was used to investigate the role of MRN GABA in stress-induced sleep disruptions. Our results revealed that bicuculline reduced footshock-induced rapid eye movement (REM) sleep decreases. In addition, the Hcrt-induced REM sleep decreases were also suppressed by bicuculline. The observations suggest that bicuculline inhibits the Hcrt-mediated responses in the MRN and relieves stress-relative syndromes, such as REM sleep decrease.

並列關鍵字

hypocretin REM sleep stress median raphe nucleus GABA

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