Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure-induced c-fos expression in the hippocampus of adult rat

Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure-induced c-fos expression in the hippocampus of adult rat
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DOI:
10.1111/j.1471-4159.2005.03347.x
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发表时间:
2005-10-01
影响因子:
4.7
通讯作者:
Mihály, A
Mihály, A
中科院分区:
医学2区
文献类型:
--
作者:
Kopniczky, Z;Dobó, E;Mihály, A

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内嗅皮层(EC)提供了主要的兴奋驱动海马CA 1和下托神经元在慢性癫痫。在这里,我们分析了单侧EC(LEC)和颞叶(阿尔韦亚)路径的损害对4-氨基吡啶诱导的癫痫发作的发展和性质的影响。对自由活动大鼠的脑电图(EEG)分析表明,该病变显著增加了海马癫痫发作的潜伏期,并减少了短暂惊厥的次数。损毁LEC后,癫痫发作诱导的海马各区神经元c-fos表达均减少。免疫细胞化学分析40天后,消融LEC确定发芽的胆碱能和钙视黄蛋白的轴突到齿状分子层。离子型谷氨酸受体(iGluRs)表达的区域和亚基特异性变化进行了鉴定。虽然AMPA受体亚单位的总量保持不变,GluR 1(flop)显示在CA 1区的显着减少。NR 1和NR 2B N-甲基-D-天冬氨酸(NMDA)受体亚单位和KA-2红藻氨酸受体亚单位的增加被确定在海马的去传入层。这些结果进一步强调了侧内嗅区在海马癫痫发作的传播和调节中的重要性,并突出了传入神经的重新连接和海马惊厥活动中齿状回iGluRs重排的潜在作用。
The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurones in chronic epilepsy. Here we analysed the effects of one-sided lateral EC (LEC) and temporoammonic (alvear) path lesion on the development and properties of 4-aminopyridine-induced seizures. Electroencephalography (EEG) analysis of freely moving rats identified that the lesion increased the latency of the hippocampal seizure significantly and decreased the number of brief convulsions. Seizure-induced neuronal c-fos expression was reduced in every hippocampal area following LEC lesion. Immunocytochemical analysis 40 days after the ablation of the LEC identified sprouting of cholinergic and calretinin-containing axons into the dentate molecular layer. Region and subunit specific changes in the expression of ionotropic glutamate receptors (iGluRs) were identified. Although the total amount of AMPA receptor subunits remained unchanged, GluR1(flop) displayed a significant decrease in the CA1 region. An increase in NR1 and NR2B N-methyl-D-aspartate (NMDA) receptor subunits and KA-2 kainate receptor subunit was identified in the deafferented layers of the hippocampus. These results further emphasize the importance of the lateral entorhinal area in the spread and regulation of hippocampal seizures and highlight the potential role of the rewiring of afferents and rearrangement of iGluRs in the dentate gyrus in hippocampal convulsive activity.