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標題: 以果蠅動物模型研究咖啡的抗氧化能力及對睡眠與睡眠剝奪後學習記憶的影響
Effects of Coffee on Anti-oxidation and Learning and Memory after Sleep Deprivation in Drosophila Models
作者: 王神寶
Shen-Pao Wang
關鍵字: coffee;caffeine;antioxidant;sleep;sleep deprivation;learning and memory;Drosophila;咖啡;咖啡因;抗氧化;睡眠;睡眠剝奪;學習記憶;果蠅
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As one of the world's most consumed beverage, the benefits of coffee to human health has gradually emerged in recent studies. Caffeine, the most widely used psychoactive drug in the world, has been mainly used to improve the efficiency of working and studying for people lacking sleep, eliminating fatigue and reduce the risk for drivers and high-risk operations under sleepiness. Recent authoritative survey in humans demonstrated that in addition to these effects, coffee also has a variety of beneficial effects on human health, including anti-oxidation, reducing the incidence and mortality of human diseases, delaying cognitive impairment in patients with Alzheimer's disease, and extending lifespan. In USA, it was found that coffee is the number one diet resource of anti-oxidants, far more than any other food and beverage. A 13-year long joint investigation by NIH and the American Association of Retired People confirmed that drinking 4-5 cups of coffee per day can reduce the mortality rate of up to 12-16% among the normal population, and up to 25 % among the people with diabetes. Coffee is found to positively regulate various systems, including the cardiovascular system, digestive system, urinary system, nervous system, immune system, etc. However, most previous studies have mainly focused on the effect of caffeine, while the animal experimental studies for coffee itself are limited. In this study, we used Drosophila as an animal model to study the impact of coffee on anti-oxidation, learning and memory after sleep deprivation, and on sleep and sleep homeostasis regulation following sleep deprivation.
Firstly, the results showed that coffee enhanced flies' tolerance to starvation and resistance to oxidative stress caused by hydrogen peroxide to certain extent, and the effect was more obvious in female flies, and the dose of 5 mg/ml (equivalent of two cups of coffee/day for humans) was the most effective. The finding is consistent with the reports that coffee is more effective for women in extending lifespan and delays the cognitive deficits of Alzheimer's disease patients, suggesting that coffee may have more significant beneficial effects on women's health. The antioxidant effects of coffee at low doses may be related to caffeine and other antioxidation components, such as caffeic acid, phytochemicals, ferulic acid, trigonelline, flavonoids and phenolic compounds such as chlorogenic acid. However, its antioxidant effect disappearred at high doses, probably because caffeine is a natural insecticide at high doses. Secondly, coffee significantly improved the 3 h-memory impairments in Drosophila after sleep deprivation, with high efficacy, as only a small dose (1.25 mg / ml) was required to confer dramatic improvement, while the dosage of 10 mg/mL produced the best effect. Thirdly, both coffee and caffeine enhanced long-term synaptic depression (LTD) in Drosophila. Fourthly, low doses of caffeine and coffee, enhanced and stabilized sleep at night. Lastly, after sleep deprivation, low or high dose of caffeine or coffee allowed fruit flies stay awake (with high doses of caffeine producing stronger effects) and maintained homeostatic sleep regulation at nighttime. The effects of coffee on improving memory impairments after sleep deprivation and enhancing long-term synaptic plasticity and sleep regulation are possibly mediated by caffeine, but these effects are relatively mild as compared with those of caffeine. The other components of coffee may help balance the stimulating effect of caffeine. Furthermore, the effects of coffee and caffeine in sleep regulation and improvement of memory deficits after sleep deprivation may be related to their anti-oxidative effects.

咖啡作爲世界上飲用最多的飲料之一,其對人類健康的益處在近年來的研究中已逐漸浮現。咖啡所含的咖啡因是世界上使用最廣的精神刺激藥物,其應用已經有較長的歷史,主要用於改善睡眠不足人群的工作學習效率,解除疲勞,並免除嗜睡狀態下所造成的危險操作的損失。而最近在人類的科學調查研究發現,除了上述作用外,咖啡還具有多種對人類健康的有益效果,包括抗氧化、降低人類疾病的發生率和死亡率、延緩早老性癡呆症患者的認知障礙,並延長正常人群的壽命。一項研究顯示,咖啡是美國第一位的食物抗氧化劑來源,遠遠超過其它飲食。據美國國立衛生研究院(NIH) 與美國退休人員協會的13年的長期大型聯合調查證實,每天喝4-5杯咖啡,可以降低正常人群的死亡率達12-16%,降低糖尿病人群的死亡率達25%。咖啡對身體多種系統都具有正向的調節作用,包括心血管系統、消化系統、泌尿系統、神經系統、免疫系統等。但是,以往的大多數研究主要研究了咖啡因的作用,而對於咖啡本身的動物實驗研究比較有限。本研究以果蠅作爲動物模型,研究咖啡對抗氧化、對睡眠剝奪後的學習記憶、以及對於睡眠和睡眠剝奪後的睡眠穩態調節的的影響。
結果顯示,第一,咖啡可以一定程度的增強果蠅對飢餓的耐受力以及抗過氧化氫造成的氧化壓力的能力,這一效果對於雌性果蠅更爲明顯,而以5 mg/ml (相當於人類 每日兩杯咖啡)的劑量效果較佳。這一發現與國際上的報導,咖啡對於女性的壽命延長以及延緩早老性癡呆的作用,是一致的,表明咖啡可能對女性健康的有益作用更爲顯著。咖啡在低劑量時的抗氧化壓力效應,除與咖啡因有關外,與咖啡中的多種抗氧化成分,如咖啡酸、植化素、阿奎酸、類黃酮化合物、綠原酸等酚類化合物、以及葫蘆巴鹼等有關聯;而在高劑量咖啡時,其抗氧化效果消失,可能因爲咖啡因在高劑量時具有殺蟲效果。第二,咖啡可以明顯改善甚至恢復睡眠剝奪後果蠅的3小時記憶力障礙,而且只需很小的劑量(1.25 mg/ml)就有很好的效果,而以 10 mg/ml 的效果最好。第三,咖啡與咖啡因均增強果蠅神經信號傳遞的長時程突觸抑制。第四,低劑量的咖啡因與咖啡,具有增強並穩定夜間睡眠的作用。第五,睡眠剝奪後,低或高劑量的咖啡因或咖啡都可以使果蠅保持清醒狀態 (以高劑量的咖啡因效果更明顯),而在夜間果蠅保持睡眠的穩態調節。咖啡對睡眠的調節以及睡眠剝奪後的記憶力的影響,以及對神經信號傳遞的突觸可塑性的增強效應,很可能主要通過其中的咖啡因起作用,並可能與其抗氧化壓力的效應有關。但是與咖啡因相比,咖啡的作用較爲溫和,可能咖啡中的其它成分能平衡咖啡因的刺激作用。
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