Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose
Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose
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DOI：
10.1046/j.1528-1157.2001.17601.x
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发表时间：
2001-11-01
期刊：
影响因子：
5.6
通讯作者：
Seyfried, TN
中科院分区：
文献类型：
--
作者：
Greene, AE;Todorova, MT;Seyfried, TN
目的：热量限制（CR）涉及喂养不足，长期以来一直被认为是改善健康和延长寿命的饮食疗法。与严重的禁食或饥饿相反，CR减少了总的食物摄入量，而不会导致营养缺乏。虽然自古希腊时代起禁食就被认为是一种有效的抗癫痫治疗方法，但禁食抑制癫痫发作的机制仍然不清楚。CR对癫痫发作易感性的影响进行了研究，在青少年（30天）和成人（70天）年龄在EL小鼠，多因素特发性epilepsy.Methods的遗传模型：青少年EL小鼠被分成两组，并喂标准的实验室食物随意（对照，n = 18）或与15%CR饮食（治疗，n = 17）。成年EL小鼠分为三组：对照组（n = 15）、15%CR组（n = 6）和30%CR组（n = 3）。在10周的治疗期内测量体重、癫痫发作易感性以及血糖和酮（β-羟基丁酸酯）水平。结果：CR能延迟癫痫发作，降低青少年和成人癫痫发作率，且无不良反应。此外，轻度CR（15%）在幼龄小鼠中的抗癫痫作用大于已确立的高脂肪生酮饮食。CR诱导的血糖水平的变化是预测血酮水平和癫痫susceptibility.Conclusions：我们建议，CR可能会降低癫痫易感性EL小鼠通过减少脑糖酵解能量。我们的临床前研究结果表明，CR可能是一种有效的抗癫痫饮食治疗人类癫痫发作疾病。
Purpose: Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health and increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although fasting has been recognized as an effective antiseizure therapy since the time of the ancient Greeks, the mechanism by which fasting inhibits seizures remains obscure. The influence of CR on seizure susceptibility was investigated at both juvenile (30 days) and adult (70 days) ages in the EL mouse, a genetic model of multifactorial idiopathic epilepsy.Methods: The juvenile EL mice were separated into two groups and fed standard lab chow either ad libitum (control, n = 18) or with a 15% CR diet (treated, n = 17). The adult EL mice were separated into three groups; control (n = 15), 15% CR (n = 6), and 30% CR (n = 3). Body weights, seizure susceptibility, and the levels of blood glucose and ketones (beta -hydroxybutyrate) were measured over a 10-week treatment period. Simple linear regression and multiple logistic regression were used to analyze the relations among seizures, glucose, and ketones.Results: CR delayed the onset and reduced the incidence of seizures at both juvenile and adult ages and was devoid of adverse side effects. Furthermore, mild CR (15%) had a greater antiepileptogenic effect than the well-established high-fat ketogenic diet in the juvenile mice. The CR-induced changes in blood glucose levels were predictive of both blood ketone levels and seizure susceptibility.Conclusions: We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders.