In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic Kv 1.1α knockout mice.
In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic Kv 1.1α knockout mice.
复制标题
DOI：
10.1111/epi.12603
复制
发表时间：
2014-05
期刊：
影响因子：
5.6
通讯作者：
Simeone KA
中科院分区：
文献类型：
--
作者：
Simeone TA;Samson KK;Matthews SA;Simeone KA
生酮饮食（KD）是治疗小儿难治性癫痫的有效方法，然而，KD是否改变癫痫脑产生的病理网络振荡仍不清楚。我们已经报道了癫痫Kv1.1α基因敲除（KO）小鼠海马CA 3区产生的病理性尖波（SPW）和高频振荡（HFO）与野生型相比具有更高的发生率、更长的持续时间和更快的波纹。突触活动的过度兴奋KO苔藓纤维显着降低CA 3主细胞尖峰定时的可靠性，有助于这种网络病理。此外，我们已经证明KD在KO小鼠中将癫痫发作减少了75%。在此，我们使用细胞外多电极阵列记录确定10-14天的体内KD治疗是否发挥改变KO小鼠的海马CA 3区在体外产生的自发SPW-HFO复合物的疾病改善作用。我们发现KD治疗显著减弱了KO SPW和波纹的病理特征，并降低了快速波纹的发生率。KD还改善了KO CA 3主细胞的尖峰定时可靠性，降低苔藓纤维兴奋性，增加苔藓纤维-CA 3配对脉冲比，并减少CA 3区域的EPSP-尖峰耦合。总的来说，这些数据表明KD治疗通过抑制过度活跃的苔藓纤维突触来调节CA 3产生的病理振荡。
The ketogenic diet (KD) is an effective therapy for pediatric refractory epilepsies, however, whether the KD changes the pathologic network oscillations generated by an epileptic brain remains unknown. We have reported that hippocampal CA3 regions of epileptic Kv1.1α knockout (KO) mice generate pathologic sharp waves (SPWs) and high frequency oscillations (HFOs) that have higher incidence, longer duration and fast ripples compared to wild-type. Synaptic activity of hyperexcitable KO mossy fibers significantly decreased CA3 principal cell spike-timing reliability contributing to this network pathology. Also, we have demonstrated that the KD reduces seizures by 75% in KO mice. Here, we determined whether 10-14 day in vivo KD treatment exerts disease modifying effects that alter the spontaneous SPW-HFO complexes generated by the hippocampal CA3 region of KO mice in vitro using extracellular multielectrode array recordings. We found that KD treatment significantly attenuated the pathologic features of KO SPWs and ripples and reduced the incidence of fast ripples. The KD also improved spike-timing reliability of KO CA3 principal cells, decreased mossy fiber excitability, increased mossy fiber-CA3 paired pulse ratios and reduced EPSP-spike coupling in the CA3 region. Collectively, these data indicate that KD treatment modulates CA3-generated pathologic oscillations by dampening hyperactive mossy fiber synapses.
登录
查看更多内容
影响因子：
2.2
作者：
Hallböök T;Ji S;Maudsley S;Martin B
通讯作者：
Martin B
影响因子：
5.6
作者：
Bough, KJ;Schwartzkroin, PA;Rho, JM
通讯作者：
Rho, JM
影响因子：
11.2
作者：
Bough, Kristopher J.;Wetherington, Jonathon;Dingledine, Raymond J.
通讯作者：
Dingledine, Raymond J.
影响因子：
5.6
作者：
Fenoglio-Simeone KA;Wilke JC;Milligan HL;Allen CN;Rho JM;Maganti RK
通讯作者：
Maganti RK
影响因子：
5.3
作者：
Simeone, Kristina A.;Matthews, Stephanie A.;Samson, Kaeli K.;Simeone, Timothy A.
通讯作者：
Simeone, Timothy A.