Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures
Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures
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DOI：
10.1002/cne.10622
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发表时间：
2003-05-12
影响因子：
2.5
通讯作者：
Esclapez, M
中科院分区：
文献类型：
--
作者：
Dinocourt, C;Petanjek, Z;Esclapez, M
在慢性边缘系统癫痫的匹鲁卡品模型中，已经报道了海马CA 1区GABA能中间神经元对兴奋性毒性损伤的脆弱性。然而，很少有人知道具体类型的中间神经元，在这个地区退化。为了表征这些中间神经元，我们对标记其肽或钙结合蛋白含量的不同GABA能神经元群体进行了定量分析。我们的数据表明，在毛果芸香碱处理大鼠的CA 1层的oriens中的GAD mRNA的神经元的数量减少涉及两个亚群的GABA能中间神经元：标记为生长抑素只（O-LM和bisteriorated细胞）和标记为parvalbumin只（篮和轴-轴细胞）的中间神经元。标记生长抑素/钙结合蛋白或生长抑素/小清蛋白的层oriens中间神经元被保存。早在注射毛果芸香碱诱导持续性癫痫发作后72小时，就观察到含生长抑素和小白蛋白的神经元数量减少。注射后1周和2周，在神经细胞的起始层可见大量变性的胞体，在腔隙分子层可见变性的轴突终末。此外，毛果芸香碱处理的动物的CA 1锥体细胞的轴突起始段的突触覆盖显着减少。这些结果表明，含生长抑素的神经元的损失，优先对应于与轴突投射到层陷窝-分子（O-LM细胞）的中间神经元的变性，并建议，这些神经元的死亡是主要负责在该地区的树突状抑制赤字报告。我们证明，含小清蛋白的神经元的损失对应于轴-轴细胞的死亡，这表明在该模型中，体周抑制和控制动作电位产生的机制也受损。(C)2003 Wiley-Liss，Inc.
In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA-containing neurons in the stratum oriens of CA1 in pilocarpine-treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O-LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo-axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin- and parvalbumin-containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum-moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine-treated animals. These results indicate that the loss of somatostatin-containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum-moleculare (O-LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin-containing neurons corresponds to the death of axo-axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model. (C) 2003 Wiley-Liss, Inc.