Alterations of hippocampal GABAergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy
Alterations of hippocampal GABAergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy
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DOI：
10.1002/hipo.1060.abs
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发表时间：
2001-01-01
期刊：
影响因子：
3.5
通讯作者：
Fritschy, JM
中科院分区：
文献类型：
--
作者：
André, V;Marescaux, C;Fritschy, JM
颞叶癫痫（TLE）患者海马结构兴奋性和抑制性回路的重组是导致慢性癫痫发作的基础。在这里，我们调查是否特定的GABA能系统的形态学改变可以与自发复发性癫痫发作（SRS）在大鼠锂-匹罗卡品模型TLE的发病。在用锂-匹罗卡品处理的大鼠的脑切片中进行中间神经元及其投射的标记物的免疫组织化学染色，包括小白蛋白（PV）、钙视网膜蛋白（CR）、钙结合蛋白（CB）、谷氨酸脱羧酶（GAD）和I型GABA转运蛋白（GAT 1（6和12天），或SRS发作后（治疗后10-18天）。半定量分析显示，选择性损失的中间神经元在层oriens的CAI，与减少GAT 1染色的放射层和层oriens。与此相反，在CA 3的中间神经元在很大程度上保留，虽然GAT 1染色也减少。这些变化发生在治疗后6天内，因此不充分。导致SRS。在齿状回，广泛的细胞损失发生在门。颗粒细胞周围的神经支配的PV阳性轴突显着减少，虽然损失的PV-中间神经元只是部分的。最引人注目的是，GAD和GAT 1阳性的GABA能轴突的密度在内分子层中显著增加。这种变化出现在沉默期，但在SRS动物中最明显。最后，额外的CB阳性神经元检测到在门，选择性SRS大鼠。这些结果表明，GABA能回路的改变发生在锂-匹罗卡品诱导的癫痫持续状态后的早期，并有助于癫痫的发生。特别是齿状回中GABA能轴突的重组可能有助于在沉默期期间由中间神经元损失诱导的同步性过度兴奋，导致慢性癫痫发作。海马200 1;11.452-468。(C)2001 Wiley-Liss，Inc.
Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type I GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CAI, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient. to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. in particular, the reorganization of GABAergic axons in the dentate gyrus might contribute to synchronize hyperexcitability induced by the interneuron loss during the silent period, leading to the onset of chronic seizures. Hippocampus 200 1;11.452-468. (C) 2001 Wiley-Liss, Inc.