Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration
Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration
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DOI：
10.2741/4517
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发表时间：
2017-01-01
影响因子：
3.1
通讯作者：
Camins, Antoni
中科院分区：
文献类型：
--
作者：
Auladell, Carme;de Lemos, Luisa;Camins, Antoni
在过去的几十年里，诱发啮齿动物癫痫持续状态的化学惊厥药物被广泛使用，因为它们能够复制出与颞叶癫痫(TLE)患者的神经病理和脑电特征高度相似的特征。红藻氨酸是实验模型中最常用的化学惊厥剂之一。KA给药主要导致海马区神经元丢失。由于c-jun氨基末端激酶信号通路(JNK)已被证明在KA激活后神经元死亡过程中起着关键作用，因此我们重点对JNK进行综述。在JNK的三种亚型(JNK1、JNK2、JNK3)中，JNK3广泛分布于海马区的大部分区域，而JNK1仅定位于CA3、CA4区和齿状回。在小鼠中，JNK3编码基因的破坏对KA具有神经保护作用，因为这些动物表现出癫痫发作活动的减少和海马神经元凋亡的减少。有鉴于此，JNK3可能成为未来癫痫治疗干预的一个有希望的亚细胞靶点。
Chemoconvulsants that induce status epilepticus in rodents have been widely used over the past decades due to their capacity to reproduce with high similarity neuropathological and electroencephalographic features observed in patients with temporal lobe epilepsy (TLE). Kainic acid is one of the most used chemoconvulsants in experimental models. KA administration mainly induces neuronal loss in the hippocampus. We focused the present review inthe c-Jun N-terminal kinase-signaling pathway (JNK), since it has been shown to play a key role in the process of neuronal death following KA activation. Among the three isoforms of JNK (JNK1, JNK2, JNK3), JNK3 is widely localized in the majority of areas of the hippocampus, whereas JNK1 levels are located exclusively in the CA3 and CA4 areas and in dentate gyrus. Disruption of the gene encoding JNK3 in mice renders neuroprotection to KA, since these animals showed a reduction in seizure activity and a diminution in hippocampal neuronal apoptosis. In light of this, JNK3 could be a promising subcellular target for future therapeutic interventions in epilepsy.