Epilepsy as a neurodevelopmental disorder.
Epilepsy as a neurodevelopmental disorder.
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DOI：
10.3389/fpsyt.2012.00019
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发表时间：
2012
影响因子：
4.7
通讯作者：
Caleo M
中科院分区：
文献类型：
--
作者：
Bozzi Y;Casarosa S;Caleo M
癫痫的特征是自发性反复发作，包括一组具有不同病因的综合征。癫痫发生是指大脑变得癫痫的过程，并且可能与几个因素有关，例如获得性结构性脑损伤、先天性脑畸形、神经元信号传导的改变以及神经元网络的成熟和可塑性缺陷。在这篇综述中，我们将重点关注大脑发育的改变，导致成年后的过度兴奋表型，提供动物和人类研究的例子。皮质发育的畸形（包括局灶性皮质发育不良、无脑回畸形、异位和多小脑回畸形）通常是致癫痫性的，并且是由生发区细胞增殖缺陷和/或受损的神经元迁移和分化引起的。抑制性中间神经元延迟或减少到达皮质板是癫痫发生的另一个可能原因。GABA能神经元在神经节隆起的早期发育过程中产生，并且未能向皮质迁移改变了兴奋/抑制平衡，导致异常网络过度兴奋。在兴奋性和抑制性突触的发育组装中更微妙的缺陷也与癫痫有关。例如，突触前蛋白突触蛋白和SNAP-25的突变导致突触传递和可塑性的紊乱，这是癫痫表型出现的基础。最后，有证据表明，在早期的“关键期”突触消除和重塑的缺陷可能会引发生命后期的过度兴奋。进一步阐明癫痫的发展途径对疾病预防和治疗具有重要意义。
Epilepsy is characterized by spontaneous recurrent seizures and comprises a diverse group of syndromes with different etiologies. Epileptogenesis refers to the process whereby the brain becomes epileptic and can be related to several factors, such as acquired structural brain lesions, inborn brain malformations, alterations in neuronal signaling, and defects in maturation and plasticity of neuronal networks. In this review, we will focus on alterations of brain development that lead to an hyperexcitability phenotype in adulthood, providing examples from both animal and human studies. Malformations of cortical development (including focal cortical dysplasia, lissencephaly, heterotopia, and polymicrogyria) are frequently epileptogenic and result from defects in cell proliferation in the germinal zone and/or impaired neuronal migration and differentiation. Delayed or reduced arrival of inhibitory interneurons into the cortical plate is another possible cause of epileptogenesis. GABAergic neurons are generated during early development in the ganglionic eminences, and failure to pursue migration toward the cortex alters the excitatory/inhibitory balance resulting in aberrant network hyperexcitability. More subtle defects in the developmental assembly of excitatory and inhibitory synapses are also involved in epilepsy. For example, mutations in the presynaptic proteins synapsins and SNAP-25 cause derangements of synaptic transmission and plasticity which underlie appearance of an epileptic phenotype. Finally, there is evidence that defects in synapse elimination and remodeling during early “critical periods” can trigger hyperexcitability later in life. Further clarification of the developmental pathways to epilepsy has important implications for disease prevention and therapy.