The possible role of GABAA receptors and gephyrin in epileptogenesis.
The possible role of GABAA receptors and gephyrin in epileptogenesis.
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DOI：
10.3389/fncel.2013.00113
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发表时间：
2013
影响因子：
5.3
通讯作者：
González MI
中科院分区：
文献类型：
--
作者：
González MI
术语癫痫发生是指神经元兴奋性的动态改变，其促进自发性癫痫发作的出现。颞叶癫痫是最常见的获得性癫痫，通常在脑损伤后发生，如创伤、热性惊厥、脑炎或癫痫持续状态。在癫痫前状态（也称为潜伏期或沉默期）期间，存在过多的分子，生物化学和结构变化，导致复发性自发性癫痫发作（或癫痫）的产生。这些改变对癫痫发展的具体贡献尚不清楚，但抑制作用的丧失与潜伏期检测到的兴奋性增加有关。神经元过度兴奋性的快速增加可能是由于，至少部分是由于生理活性GABAA受体（GABAAR）数量的下降。参与GABAAR运输和锚定的支架蛋白的表达改变可直接影响GABA能突触的稳定性并促进抑制性神经传递的缺陷。揭示癫痫发生过程中的分子机制及其对GABAAR和支架蛋白调节的可能影响，可能为预防癫痫的发展提供新的靶点。
The term epileptogenesis refers to a dynamic alteration in neuronal excitability that promotes the appearance of spontaneous seizures. Temporal lobe epilepsy, the most common type of acquired epilepsy, often develops after an insult to the brain such as trauma, febrile seizures, encephalitis, or status epilepticus. During the pre-epileptic state (also referred as latent or silent period) there is a plethora of molecular, biochemical, and structural changes that lead to the generation of recurrent spontaneous seizures (or epilepsy). The specific contribution of these alterations to epilepsy development is unclear, but a loss of inhibition has been associated with the increased excitability detected in the latent period. A rapid increase in neuronal hyperexcitability could be due, at least in part, to a decline in the number of physiologically active GABAA receptors (GABAAR). Altered expression of scaffolding proteins involved in the trafficking and anchoring of GABAAR could directly impact the stability of GABAergic synapses and promote a deficiency in inhibitory neurotransmission. Uncovering the molecular mechanisms operating during epileptogenesis and its possible impact on the regulation of GABAAR and scaffolding proteins may offer new targets to prevent the development of epilepsy.
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