Do structural changes in GABA neurons give rise to the epileptic state?
Do structural changes in GABA neurons give rise to the epileptic state?
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DOI：
10.1007/978-94-017-8914-1_12
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发表时间：
2014
影响因子：
--
通讯作者：
Houser CR
中科院分区：
文献类型：
--
作者：
Houser CR
确定GABA神经元在癫痫状态发展中的作用在获得性癫痫中特别困难，部分原因是在这种情况下发生的多种变化。虽然曾经受到质疑，但现在有相当多的证据表明，在获得性癫痫模型中，多个脑区的GABA神经元丢失。这种损失可能会影响几种细胞类型，包括生长抑素和小白蛋白表达的中间神经元，并且受影响最严重的细胞类型可能会因大脑区域和模型而异。由于海马和大脑皮层中GABA神经元的多样性，所导致的功能缺陷不太可能被其他亚型的剩余GABA神经元完全补偿。GABA神经元丢失在癫痫中的根本重要性得到了遗传小鼠模型中的发现的支持，其中GABA神经元似乎相对选择性地减少，并且癫痫发作易感性增加和自发性癫痫发作发展。在获得性癫痫中也会发生剩余GABA神经元的改变。这些包括可能损害功能的输入或受体的改变，以及GABA能轴突及其突触连接的形态学重组。如果正常的回路重新建立，这种轴突发芽可能是补偿性的，但异常回路的产生可能导致癫痫。因此，GABA神经元改变的功能效应可能不仅包括GABA能抑制的减少，还包括过度的神经元同步性和潜在的去极化GABA能影响。GABA神经元丢失和剩余GABA神经元的改变的组合提供了可能的，但尚未证实的，癫痫状态的底物。
Identifying the role of GABA neurons in the development of an epileptic state has been particularly difficult in acquired epilepsy, in part because of the multiple changes that occur in such conditions. Although once questioned, there is now considerable evidence for loss of GABA neurons in multiple brain regions in models of acquired epilepsy. This loss can affect several cell types, including both somatostatin- and parvalbumin-expressing interneurons, and the cell type that is most severely affected can vary among brain regions and models. Because of the diversity of GABA neurons in the hippocampus and cerebral cortex, resulting functional deficits are unlikely to be compensated fully by remaining GABA neurons of other subtypes. The fundamental importance of GABA neuron loss in epilepsy is supported by findings in genetic mouse models in which GABA neurons appear to be decreased relatively selectively, and increased seizure susceptibility and spontaneous seizures develop. Alterations in remaining GABA neurons also occur in acquired epilepsy. These include alterations in inputs or receptors that could impair function, as well as morphological reorganization of GABAergic axons and their synaptic connections. Such axonal sprouting could be compensatory if normal circuits are reestablished, but the creation of aberrant circuitry could contribute to an epileptic condition. The functional effects of GABA neuron alterations thus may include not only reductions in GABAergic inhibition but also excessive neuronal synchrony and, potentially, depolarizing GABAergic influences. The combination of GABA neuron loss and alterations in remaining GABA neurons provides likely, though still unproven, substrates for the epileptic state.