Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1-null mice.
Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1-null mice.
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DOI：
10.1111/j.1528-1167.2009.02163.x
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发表时间：
2009-09
期刊：
影响因子：
5.6
通讯作者：
Maganti RK
中科院分区：
文献类型：
--
作者：
Fenoglio-Simeone KA;Wilke JC;Milligan HL;Allen CN;Rho JM;Maganti RK
众所周知，癫痫发作会扰乱人类和癫痫动物模型的昼夜节律。然而，目前尚不清楚潜在癫痫的治疗是否会恢复正常的生物节律。我们询问：(1)癫痫发作活动的特征是昼夜节律性；(2)慢性癫痫小鼠表现出活动-休息节律受损；(3)抗惊厥药生酮饮食(KD)治疗改善了这种扰动。慢性癫痫KcNA1基因缺失小鼠喂饲标准饲料或KD 4wk，连续3-5天进行视频脑电和动态监测，以评估癫痫发作活动和休息-活动周期。KcNA1基因缺失小鼠的惊厥活动表现出昼夜节律性，在Zeitgeber(ZT)处达到峰值2.30±1.52。癫痫小鼠的活动-静息节律被显著打乱。野生型小鼠的运动活动在ZT15.45±0.28(ZT14：26-ZT16：51)达到峰值，而癫痫小鼠的运动活动更难以预测，出现在12.4小时的范围内(ZT06：33-ZT18：57)。在9只癫痫小鼠中，6只癫痫小鼠的峰值活动延迟至ZT17.42±0.38，其余小鼠的峰值活动提前至ZT10.00±1.26。KD治疗消除了癫痫发作的周期性，并将活动-休息节律恢复到与野生型小鼠相似的值(即活动峰值在ZT16.73±0.67)。Kcna1基因缺失的小鼠癫痫发作具有24小时的周期性，昼夜行为受损。KD可减少癫痫发作的次数和周期，恢复正常的行为节律，提示这种非药物疗法可能有益于癫痫患者的生物节律紊乱。
Seizures are known to perturb circadian rhythms in humans as well as in animal models of epilepsy. However, it is unknown whether treatment of the underlying epilepsy restores normal biological rhythms. We asked whether: (1) seizure activity is characterized by diurnal rhythmicity; (2) chronically epileptic mice exhibit impaired activity-rest rhythms; and (3) treatment with the anticonvulsant ketogenic diet (KD) improves such perturbations. Chronically epileptic Kcna1-null mice were fed either a standard diet or KD for 4 wks and subjected to continuous video-EEG and actigraphy monitoring for 3–5 days to assess seizure activity and rest-activity cycles. Seizure activity in Kcna1-null mice demonstrated diurnal rhythmicity, peaking at zeitgeber (ZT) 2.30±1.52. Activity-rest rhythms of epileptic mice were significantly disrupted. Whereas locomotor activity for wild-type mice peaked at ZT15.45±0.28 (ZT14:26–ZT16:51), peak activity of epileptic mice was more unpredictable, occurring over a 12.4hr range (ZT06:33–ZT18:57). In 6 of 9 epileptic mice, peak activity was delayed to ZT17.42±0.38, while peak activity was advanced to ZT10.00±1.26 in the remaining mice. Treatment with the KD abolished seizure periodicity and restored the activity-rest rhythm to values resembling those of wild-type mice (i.e. activity peaking at ZT16.73±0.67). Kcna1-null mice experience seizures with 24-hr periodicity and impaired circadian behavior. KD reduces the number and periodicity of seizures and restores normal behavioral rhythms, suggesting that this non-pharmacological therapy may benefit biological rhythm disturbances in epileptic patients.
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影响因子：
4.7
作者：
Ferrillo, F;Beelke, M;Nobili, L
通讯作者：
Nobili, L
影响因子：
2.9
作者：
Quigg, M;Straume, M;Bertram, EH
通讯作者：
Bertram, EH
影响因子：
5.6
作者：
SCHAPEL, GJ;BERAN, RG;MATTHEWS, CD
通讯作者：
MATTHEWS, CD
DOI：
10.1016/s0165-3806(01)00213-9
发表时间：
2001-08-23
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Szot, P;Weinshenker, D;Schwartzkroin, PA
通讯作者：
Schwartzkroin, PA
影响因子：
9.9
作者：
Bazil, CW;Short, D;Zheng, W
通讯作者：
Zheng, W