Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy.
Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy.
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DOI：
10.3389/fneur.2018.00632
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发表时间：
2018
影响因子：
3.4
通讯作者：
Gitaí DLG
中科院分区：
文献类型：
--
作者：
Matos HC;Koike BDV;Pereira WDS;de Andrade TG;Castro OW;Duzzioni M;Kodali M;Leite JP;Shetty AK;Gitaí DLG
从边缘癫痫的振荡模式、白天对癫痫发作的影响以及抗癫痫药物的疗效来看，内侧颞叶癫痫(MTLE)与昼夜节律控制的相互作用是明显的。此外，癫痫发作本身会干扰生物节律输出，包括体温、运动活动、脑电模式和转录组的昼夜振荡。然而，这种串扰背后的分子机制仍不清楚。在这项研究中，我们系统地评估了七个核心昼夜节律转录本(BMal1、Clock、Cry1、Cry2、PER1、PER2和PER3)在MTLE癫痫持续状态(SE)模型中的时间表达和自发运动活动(SLA)。SE后各组的24小时振荡SLA保持不变，尽管SE后早期和癫痫时相的昼夜节律、活动量和强度都发生了变化。致痫过程中SLA节律的峰期延迟，发作时出现24小时节律碎片化和活动期延长。昼夜节律转录产物BMal1、Cry1、Cry2、PER1、PER2和PER3的时间表达也发生了显著变化。致痫大鼠BMal1的表达维持在振荡状态，但幅度较低(A=0.2)，且在癫痫发作时处于较高的峰期。在癫痫发作早期，Cry1和Cry2的昼夜节律消失，但在癫痫期恢复。PER1和PER2的节律性表达在SE后组中被破坏，而PER3仅在癫痫时相呈现心律失常的特征。Clock的表达在任何情况下都不呈现节律性模式。这些核心时钟基因的振荡模式可能有助于海马区的24小时循环，从而导致癫痫发作的周期性。此外，通过收集6个不同Zeitgeber Times(ZT)的样本，我们发现除PER3和PER2外，所有时钟转录本在SE诱导后都显著失调。总体而言，癫痫发作后早期和癫痫时相SLA节律的改变暗示癫痫发作可能是一种非光信号，这可能与激活海马-伏隔神经通路有关。另一方面，SE后时钟基因在时间上的表达变化表明它们参与了MTLE。
The interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system control is apparent from an oscillatory pattern of limbic seizures, daytime's effect on seizure onset and the efficacy of antiepileptic drugs. Moreover, seizures per se can interfere with the biological rhythm output, including circadian oscillation of body temperature, locomotor activity, EEG pattern as well as the transcriptome. However, the molecular mechanisms underlying this cross-talk remain unclear. In this study, we systematically evaluated the temporal expression of seven core circadian transcripts (Bmal1, Clock, Cry1, Cry2, Per1, Per2, and Per3) and the spontaneous locomotor activity (SLA) in post-status epilepticus (SE) model of mTLE. Twenty-four hour oscillating SLA remained intact in post-SE groups although the circadian phase and the amount and intensity of activity were changed in early post-SE and epileptic phases. The acrophase of the SLA rhythm was delayed during epileptogenesis, a fragmented 24 h rhythmicity and extended active phase length appeared in the epileptic phase. The temporal expression of circadian transcripts Bmal1, Cry1, Cry2, Per1, Per2, and Per3 was also substantially altered. The oscillatory expression of Bmal1 was maintained in rats imperiled to SE, but with lower amplitude (A = 0.2) and an advanced acrophase in the epileptic phase. The diurnal rhythm of Cry1 and Cry2 was absent in the early post-SE but was recovered in the epileptic phase. Per1 and Per2 rhythmic expression were disrupted in post-SE groups while Per3 presented an arrhythmic profile in the epileptic phase, only. The expression of Clock did not display rhythmic pattern in any condition. These oscillating patterns of core clock genes may contribute to hippocampal 24 h cycling and, consequently to seizure periodicity. Furthermore, by using a pool of samples collected at 6 different Zeitgeber Times (ZT), we found that all clock transcripts were significantly dysregulated after SE induction, except Per3 and Per2. Collectively, altered SLA rhythm in early post-SE and epileptic phases implies a possible role for seizure as a nonphotic cue, which is likely linked to activation of hippocampal–accumbens pathway. On the other hand, altered temporal expression of the clock genes after SE suggests their involvement in the MTLE.
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影响因子：
16.2
作者：
Cao R;Robinson B;Xu H;Gkogkas C;Khoutorsky A;Alain T;Yanagiya A;Nevarko T;Liu AC;Amir S;Sonenberg N
通讯作者：
Sonenberg N
影响因子：
16.6
作者：
Barca-Mayo O;Pons-Espinal M;Follert P;Armirotti A;Berdondini L;De Pietri Tonelli D
通讯作者：
De Pietri Tonelli D
影响因子：
5.3
作者：
Cho CH
通讯作者：
Cho CH
影响因子：
5.6
作者：
Coulter, DA
通讯作者：
Coulter, DA
影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S