Post-ictal Generalized EEG Suppression is reduced by Enhancing Dorsal Raphe Serotonergic Neurotransmission.
Post-ictal Generalized EEG Suppression is reduced by Enhancing Dorsal Raphe Serotonergic Neurotransmission.
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DOI：
10.1016/j.neuroscience.2020.11.029
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发表时间：
2021-01-15
期刊：
影响因子：
3.3
通讯作者：
Buchanan GF
中科院分区：
文献类型：
--
作者：
Petrucci AN;Joyal KG;Chou JW;Li R;Vencer KM;Buchanan GF
癫痫猝死（SUDEP）是难治性癫痫患者死亡的主要原因。SUDEP的一个拟议的风险标志是发作后全身性EEG抑制（PGES）的持续时间。PGES的潜在机制尚不清楚。5-羟色胺（5-HT）与SUDEP的病理生理学有关。癫痫发作抑制中缝背核（DRN）中5-HT神经元的活性。我们假设，抑制DRN 5-HT神经元活动有助于PGES，增加5-HT神经传递或在癫痫发作前刺激DRN会减少PGES持续时间。成年C57 BL/6 J和Pet 1-Cre小鼠接受EEG/EMG电极，右基底外侧杏仁核中的双极刺激/记录电极，以及微透析引导插管或腺相关病毒（AAV）注射，允许通道视紫红质2表达加上光纤进入DRN。全身应用选择性5-HT再摄取抑制剂西酞普兰（20 mg/kg）可减少清醒（n = 23）和非快速眼动（NREM）睡眠（n = 13）期间诱发癫痫发作的PGES持续时间，而氟西汀（10 mg/kg）预处理可减少清醒（n = 11）诱发癫痫发作后的PGES持续时间，但对NREM睡眠（n = 9）无影响。DRN的局灶性化学（n = 6）或光遗传学（n = 8）刺激减少了清醒期间诱导的点燃小鼠癫痫发作后的PGES持续时间。在PGES期间，动物表现出不动和EEG活动抑制，西酞普兰预处理可降低EEG活动抑制。提示5-HT和DRN可能参与PGES的调节。
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. A proposed risk marker for SUDEP is the duration of post-ictal generalized EEG suppression (PGES). The mechanisms underlying PGES are unknown. Serotonin (5-HT) has been implicated in SUDEP pathophysiology. Seizures suppress activity of 5-HT neurons in the dorsal raphe nucleus (DRN). We hypothesized that suppression of DRN 5-HT neuron activity contributes to PGES and increasing 5-HT neurotransmission or stimulating the DRN before a seizure would decrease PGES duration. Adult C57BL/6J and Pet1-Cre mice received EEG/EMG electrodes, a bipolar stimulating/recording electrode in the right basolateral amygdala, and either a microdialysis guide cannula or an injection of adeno-associated virus (AAV) allowing expression of channelrhodopsin2 plus an optic fiber into the DRN. Systemic application of the selective 5-HT reuptake inhibitor citalopram (20 mg/kg) decreased PGES duration from seizures induced during wake (n = 23) and non-rapid eye movement (NREM) sleep (n = 13) whereas fluoxetine (10 mg/kg) pretreatment decreased PGES duration following seizures induced from wake (n = 11), but not NREM sleep (n = 9). Focal chemical (n = 6) or optogenetic (n = 8) stimulation of the DRN reduced PGES duration following seizures in kindled mice induced during wake. During PGES, animals exhibited immobility and suppression of EEG activity that was reduced by citalopram pretreatment. These results suggest 5-HT and the DRN may regulate PGES.
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DOI：
10.1016/s1474-4422(12)70188-6
发表时间：
2012-09
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Blumenfeld H
通讯作者：
Blumenfeld H
影响因子：
3.7
作者：
Auerbach DS;Jones J;Clawson BC;Offord J;Lenk GM;Ogiwara I;Yamakawa K;Meisler MH;Parent JM;Isom LL
通讯作者：
Isom LL
羟色胺神经元具有抗惊厥作用，可降低癫痫发作引起的死亡率
影响因子：
5.5
作者：
Buchanan, Gordon F.;Murray, Nicholas M.;Richerson, George B.
通讯作者：
Richerson, George B.
影响因子：
16.6
作者：
Bender F;Gorbati M;Cadavieco MC;Denisova N;Gao X;Holman C;Korotkova T;Ponomarenko A
通讯作者：
Ponomarenko A
影响因子：
14.5
作者：
Englot, Dario J.;Yang, Li;Blumenfeld, Hal
通讯作者：
Blumenfeld, Hal