Immature neurons and GABA networks may contribute to epileptogenesis in pediatric cortical dysplasia
Immature neurons and GABA networks may contribute to epileptogenesis in pediatric cortical dysplasia
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DOI：
10.1111/j.1528-1167.2007.01293.x
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发表时间：
2007-01-01
期刊：
影响因子：
5.6
通讯作者：
Mathern, Gary W.
中科院分区：
文献类型：
--
作者：
Cepeda, Carlos;Andre, Veronique M.;Mathern, Gary W.
皮质发育不良（cortical dysplasia，CD）是小儿癫痫手术患者常见的病理基础，与未成熟皮质有许多相似之处，如N-甲基-D-天冬氨酸（NMDA）受体对Mg 2+的敏感性降低，亚板样神经元和未分化细胞的持续存在。由于γ-氨基丁酸（GABA）是早期皮质发育中的主要神经递质，我们假设CD组织中GABA受体介导的突触功能增加。红外视频显微镜和全细胞膜片钳记录被用来表征未成熟和正常外观的神经元的形态和电生理学特性的切片皮质组织样本切除治疗儿童（0.2-14岁）的耐药性癫痫。此外，我们还研究了自发和诱发的突触活动，以及对外源性GABA应用的反应。我们证明了年轻的CD组织中存在未成熟的锥体神经元和网络，以及GABA突触活动的优势。此外，自发性GABA去极化经常诱导动作电位，支持GABA在CD中的潜在兴奋作用。诱发的GABA介导的突触反应也是突出的，和浴应用4-氨基吡啶诱导的节律性去极化被荷包牡丹碱阻断。最后，与轻度和非CD病例相比，对外源性应用GABA的反应在重度中具有去极化逆转电位。目前的数据支持这一假设，CD共享未成熟皮层的功能，主要的和潜在的兴奋性GABA（A）受体介导的神经传递。这些结果可以部分解释儿童CD中皮质网络兴奋性增加。
Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has a number of similarities with immature cortex, such as reduced Mg2+ sensitivity of N-methyl-D-aspartate (NMDA) receptors and the persistence of subplate-like neurons and undifferentiated cells. Because gamma-aminobutyric acid (GABA) is the main neurotransmitter in early cortical development, we hypothesized increased GABA receptor-mediated synaptic function in CD tissue. Infrared videomicroscopy and whole-cell patch clamp recordings were used to characterize the morphology and electrophysiological properties of immature and normal-appearing neurons in slices from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy in children (0.2-14 years). In addition, we examined spontaneous and evoked synaptic activity, as well as responses to exogenous GABA application. We demonstrate both the presence of immature pyramidal neurons and networks in young CD tissue and the predominance of GABA synaptic activity. In addition, spontaneous GABA depolarizations frequently induced action potentials, supporting a potential excitatory role of GABA in CD. Evoked synaptic responses mediated by GABA were also prominent, and bath application of 4-aminopyridine induced rhythmic depolarizations that were blocked by bicuculline. Finally, responses to exogenous application of GABA had depolarized reversal potentials in severe compared to mild and non-CD cases. The present data support the hypothesis that CD shares features of immature cortex, with predominant and potentially excitatory GABA(A) receptor-mediated neurotransmission. These results could partially explain the increased excitability of the cortical network in pediatric CD.