Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.
Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.
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DOI：
10.1111/ejn.13137
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发表时间：
2016-06
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影响因子：
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通讯作者：
Kiyatkin EA
中科院分区：
文献类型：
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作者：
Wakabayashi KT;Spekterman L;Kiyatkin EA
葡萄糖是细胞活动的主要代谢底物，必须输送到大脑以实现正常的神经功能。葡萄糖也是一种独特的代谢物，除了所有天然糖都具有的有益的感官特性和代谢作用外，葡萄糖还能穿过血脑屏障，作用于多个脑细胞上表达的葡萄糖受体。为了阐明这种直接葡萄糖作用在大脑中的作用，我们比较了葡萄糖与果糖（一种更甜但代谢等效的糖）诱导的神经和行为效应。首先，通过在自由活动的大鼠中使用基于酶的生物传感器，我们证实了葡萄糖在静脉注射后以剂量依赖性方式在延髓核中迅速增加。相比之下，果糖只在大剂量注射后才引起最小的反应。第二，我们发现，在不受限制的访问期间，幼稚大鼠消耗的葡萄糖比果糖溶液体积更大;差异出现在初始暴露期间具有一定的潜伏期，并在随后的测试中强烈增加。当同等糖经验的大鼠以交替顺序提供葡萄糖或果糖时，这两种物质的消耗最初是相等的，但在随后的会议中只有葡萄糖的消耗增加。最后，具有相同葡萄糖-果糖经验的大鼠在两瓶选择过程中对葡萄糖产生了强烈的偏好;在最初的测试中，这种效果出现了一定的潜伏期，并在随后的测试中大大放大。我们的研究结果表明，葡萄糖直接进入大脑及其对脑细胞的后续影响可能是葡萄糖消耗的经验依赖性升级和葡萄糖偏好超过果糖的发展的关键。虽然葡萄糖和果糖的热量相等，果糖比葡萄糖甜，但大鼠在反复自由饮用期间表现出葡萄糖消耗量不断增加，并对葡萄糖产生偏好。这些行为现象似乎与葡萄糖进入大脑及其对葡萄糖敏感的中枢神经元的作用有关。葡萄糖的这种神经效应可能在调节含糖产品和可能不同食物的消费行为中至关重要。
Glucose, a primary metabolic substrate for cellular activity, must be delivered to the brain for normal neural functions. Glucose is also a unique reinforcer—besides its rewarding sensory properties and metabolic effects, which all natural sugars have, glucose crosses the blood-brain barrier and acts on glucoreceptors expressed on multiple brain cells. To clarify the role of this direct glucose action in the brain, we compared neural and behavioral effects of glucose with those induced by fructose, a sweeter yet metabolically equivalent sugar. First, by using enzyme-based biosensors in freely moving rats, we confirmed that glucose rapidly increases in the nucleus accumbens in a dose-dependent manner after its intravenous delivery. In contrast, fructose induced a minimal response only after a large-dose injection. Second, we showed that naive rats during unrestricted access consume larger volumes of glucose than fructose solution; the difference appeared with a definite latency during the initial exposure and strongly increased during subsequent tests. When rats with equal sugar experience were presented with either glucose or fructose in alternative order, consumption of both substances was initially equal, but only consumption of glucose increased during subsequent sessions. Finally, rats with equal glucose-fructose experience developed a strong preference of glucose over fructose during a two-bottle choice procedure; the effect appeared with a definite latency during the initial test and greatly amplified during subsequent tests. Our results suggest that direct entry of glucose in the brain and its subsequent effects on brain cells could be critical for the experience-dependent escalation of glucose consumption and the development of glucose preference over fructose. While glucose and fructose are calorically equal and fructose is sweeter than glucose, rats exhibit escalating glucose consumption and develop preference of glucose over fructose during repeated sessions of free drinking. These behavioral phenomena appear to be related to glucose entry to the brain and its action on glucose-sensitive central neurons. This neural effect of glucose could be critical in regulating consummatory behaviors with both sugary product and possibly different foods.