Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats.
Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats.
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DOI：
10.14814/phy2.12411
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发表时间：
2015-05
影响因子：
2.5
通讯作者：
Masino SA
中科院分区：
文献类型：
--
作者：
Blaise JH;Ruskin DN;Koranda JL;Masino SA
生酮饮食是低碳水化合物、充足蛋白质、高脂肪的饮食，具有抗惊厥活性，主要用于治疗小儿癫痫。抗惊厥机制被认为涉及提高抑制和/或以其他方式限制大脑中的兴奋性。然而，这种机制也可能显著影响正常的大脑活动并限制突触可塑性，这些影响在发育中的大脑中非常重要。为了评估生酮饮食对突触传递和可塑性的影响，在清醒、自由行为的幼年雄性大鼠的穿通通路/齿状回突触处进行电生理记录。在记录前1周植入电极。在记录前，动物自由进食常规食物或生酮饮食3周。虽然生酮饮食没有显著改变基线兴奋性（通过输入-输出曲线评估）或短期可塑性（使用成对脉冲比），但它确实降低了所有刺激后时间点的长时程增强幅度，直到最后一次测量（48 h）。结果表明，生酮饮食喂养的诱导幅度的影响，但不维持长时程增强。饮食对基线传输和成对脉冲比缺乏影响表明，在强刺激条件下优先限制兴奋的机制与生酮饮食抑制癫痫发作而对正常大脑活动无重大影响的临床报告一致。限制癫痫易感网络的可塑性可能会限制癫痫诱导的癫痫发生，这可能有助于生酮饮食在癫痫中的持续获益。
Ketogenic diets are low-carbohydrate, sufficient protein, high-fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely-behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input–output curves) or short-term plasticity (using the paired-pulse ratio), it did reduce the magnitude of long-term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet-feeding on the induction magnitude but not the maintenance of long-term potentiation. The lack of effect of the diet on baseline transmission and the paired-pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure-susceptible network may limit seizure-induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy.