Caloric restriction augments brain glutamic acid decarboxylase-65 and-67 expression
Caloric restriction augments brain glutamic acid decarboxylase-65 and-67 expression
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DOI：
10.1002/jnr.20144
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发表时间：
2004-07-15
影响因子：
4.2
通讯作者：
Bondy, CA
中科院分区：
文献类型：
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作者：
Cheng, CM;Hicks, K;Bondy, CA
生酮饮食是一种非常低碳水化合物、高脂肪的饮食，用于治疗难治性癫痫。我们假设这种饮食可能通过增加谷氨酸脱羧酶（GAD）的表达而起作用，GAD是γ-氨基丁酸（GABA）合成的限速酶。因此，我们在一个成熟的、抑制食欲的生酮饮食啮齿动物模型中评价了脑GAD水平。因为当给予适度（类似于10%）热量限制时饮食是最有效的，我们研究了三组动物：自由进食标准大鼠食物（Ad lib-Std）;热量限制的标准食物（CR-Std）;和等热量、热量限制的生酮饮食（CR-Ket）。我们发现，与对照组相比，两个CR饮食组的下丘和上级丘以及小脑皮质中的GAD 67 mRNA显著增加（例如，在上级丘和小脑皮质分别为45%和71%（P <0.001）。与随意对照组相比，CR-Std和CR-Ket饮食组的上级丘和颞叶皮质中GAD 65 mRNA选择性增加。唯一明显的CR-Ket特异性效应是纹状体中GAD 67 mRNA增加30%（P = .03）。增强GAD免疫反应检测到平行的mRNA的变化。这些数据清楚地表明，热量限制会增加多个大脑区域的大脑GAD 65和-67表达，而与生酮效应无关。这些观察结果可以解释为什么热量限制提高生酮饮食治疗癫痫的疗效，并表明饮食调整可能有助于治疗以GAD或GABA活性受损为特征的许多脑部疾病。(C)2004 Wiley-Liss，Inc.
The ketogenic diet is a very low-carbohydrate, high-fat diet used to treat refractory epilepsy. We hypothesized that this diet may act by increasing expression of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in gamma-aminobutyric acid (GABA) synthesis. Thus, we evaluated brain GAD levels in a well-established, seizuresuppressing, rodent model of the ketogenic diet. Because the diet is most effective when administered with a modest (similar to10%) calorie restriction, we studied three groups of animals: rats fed ad libitum standard rat chow (Ad lib-Std); calorie-restricted standard chow (CR-Std); and an isocaloric, calorie-restricted ketogenic diet (CR-Ket). We found that GAD67 mRNA was significantly increased in the inferior and superior colliculi and cerebellar cortex in both CR diet groups compared with control (e.g., by 45% in the superior colliculus and by 71% in the cerebellar cortex; P < .001). GAD65 mRNA was selectively increased in the superior colliculus and temporal cortex in both CR-Std and CR-Ket diet groups compared with ad lib controls. The only apparent CR-Ket-specific effect was a 30% increase in GAD67 mRNA in the striatum (P = .03). Enhanced GAD immunoreactivity was detected in parallel with the mRNA changes. These data clearly show that calorie restriction increases brain GAD65 and -67 expression in several brain regions, independent of ketogenic effects. These observations may explain why caloric restriction improves the efficacy of the ketogenic diet in treating epilepsy and suggest that diet modification might be useful in treatment of a number of brain disorders characterized by impaired GAD or GABA activity. (C) 2004 Wiley-Liss, Inc.