Transition to absence seizures and the role of GABA(A) receptors.

Transition to absence seizures and the role of GABA(A) receptors.
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DOI:
10.1016/j.eplepsyres.2011.07.011
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发表时间:
2011-12
期刊:
影响因子:
2.2
通讯作者:
Terry, John R.
Terry, John R.
中科院分区:
医学4区
文献类型:
--
作者:
Crunelli, Vincenzo;Cope, David W.;Terry, John R.

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失神发作似乎是在一个假定的皮质“起始位点”启动的表达中等振幅的5-9 Hz振荡,这可能部分是由于减少相位GABAA受体功能。这些振荡迅速传播到其他皮层区域和丘脑,导致全面发展的普遍性尖峰和波放电。在遗传模型的丘脑皮质神经元中,阶段性GABAA抑制是不变的或增加的,而紧张性GABAA抑制在遗传和药理学模型中均增加。这种增强的紧张性抑制是失神发作产生所必需的,并且在遗传模型中,它是由星形胶质细胞GABA转运蛋白GAT-1的功能障碍引起的。来自近交系和转基因动物的矛盾结果仍然不允许我们得出明确的结论,在丘脑网状核的GABA能神经元的阶段性GABAA抑制的变化。数学建模可以提高我们对这些相互竞争的假设的理解,通过允许调查它们的机制方面,从而使我们能够更好地了解癫痫发作的产生和演变的过程。
Absence seizures appear to be initiated in a putative cortical ‘initiation site’ by the expression of medium-amplitude 5–9 Hz oscillations, which may in part be due to a decreased phasic GABAA receptor function. These oscillations rapidly spread to other cortical areas and to the thalamus, leading to fully developed generalized spike and wave discharges. In thalamocortical neurons of genetic models, phasic GABAA inhibition is either unchanged or increased, whereas tonic GABAA inhibition is increased both in genetic and pharmacological models. This enhanced tonic inhibition is required for absence seizure generation, and in genetic models it results from a malfunction in the astrocytic GABA transporter GAT-1. Contradictory results from inbred and transgenic animals still do not allow us to draw firm conclusions on changes in phasic GABAA inhibition in the GABAergic neurons of the nucleus reticularis thalami. Mathematical modelling may enhance our understanding of these competing hypotheses, by permitting investigations of their mechanistic aspects, hence enabling a greater understanding of the processes underlying seizure generation and evolution.
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