Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus
Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus
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DOI：
10.1093/brain/awh004
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发表时间：
2004-01-01
期刊：
影响因子：
14.5
通讯作者：
DeFelipe, J
中科院分区：
文献类型：
--
作者：
Arellano, JI;Muñoz, A;DeFelipe, J
GABA介导的抑制受损是解释癫痫发作活动的主要假设之一，无论是在实验模型中还是在人类癫痫中。本文研究了正常人和癫痫病人海马结构中某些GABA能回路的分布和神经化学特征。我们把注意力主要集中在枝形细胞上，因为它们与篮状细胞一起被认为对锋电位的产生具有强大的影响。枝状细胞是一种独特的中间神经元，其轴突终末（Ch-终末）与皮质锥体细胞和齿状回颗粒细胞的轴突起始段形成突触。不同的神经化学亚群的枝形细胞已被确定免疫细胞化学，主要是在新皮层。Ch末端的标记物包括GABA转运蛋白1（GAT-1）、细胞表面糖蛋白神经细胞粘附分子（PSA-NCAM）的多唾液酸化形式以及钙结合蛋白小清蛋白（PV）和钙结合蛋白D-28 k（CB）。在正常的海马结构，GAT-1和PV-免疫反应（-IR）的CH-终端被确定在齿状回的颗粒和多态性层，在地层的CA字段的oriens和，并在锥体层的下托复合体。此外，与海马和齿状回相反，正常下托的上锥体层中的Ch-末端的子集表达CB和PSA-NCAM。癫痫患者的海马结构呈现出令人印象深刻的形态学和神经化学重组的CH-终端和篮子的形成。这在齿状回和海马结构中是明显的，但在下托中不是，下托似乎保持不变。主要是，许多和更复杂的PV-和CB-IR CH-终端，以及密集的PV-IR篮形成，出现在一些海马段，而在其他地区有一个缺乏标记的元素。这些变化不仅在不同患者之间变化很大，而且在给定患者的不同海马区域内也变化很大。一般而言，这些变化与患者的临床特征或组织病理学变化程度无关，如颗粒细胞分散、神经元丢失和苔藓纤维增殖。然而，一些幸存的神经元在邻近地区的神经元损失的密集的篮子形成和复杂的CH-终端始终支配。这些结果表明，在人类癫痫海马中，GABA能回路比以前认为的更高度修饰。当考虑沿着其他海马外改变时，我们认为这些改变在海马硬化相关的颞叶癫痫的病理生理学中是重要的。
Impairment of GABA-mediated inhibition is one of the main hypotheses invoked to explain seizure activity, both in experimental models and in human epilepsy. We have studied the distribution and the neurochemical characteristics of certain GABAergic circuits in the normal and epileptic human sclerotic hippocampal formation. We have focused our attention mainly on chandelier cells because, together with basket cells, they are considered to have powerful effects on spike generation. Chandelier cells represent a unique type of interneuron whose axon terminals (Ch-terminals) form synapses with the axon initial segments of cortical pyramidal cells and granular cells of the dentate gyrus. Different neurochemical subpopulations of chandelier cells have been identified by immunocytochemistry, mainly in the neocortex. Markers for Ch-terminals include the GABA transporter 1 (GAT-1), the polysialylated form of the cell-surface glycoprotein neural cell adhesion molecule (PSA-NCAM) and the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB). In the normal hippocampal formation, GAT-1- and PV-immunoreactive (-ir) Ch-terminals were identified in the granular and polymorphic layers of the dentate gyrus, in the strata pyramidale and oriens of the CA fields, and in the pyramidal layer of the subicular complex. In addition, and in contrast to the hippocampus and dentate gyrus, subsets of Ch-terminals in the upper pyramidal layer of the normal subiculum express CB and PSA-NCAM. The sclerotic hippocampus of epileptic patients presented an impressive morphological and neurochemical reorganization of Ch-terminals and basket formations. This was apparent in the dentate gyrus and hippocampal formation, but not in the subiculum, which appeared to remain unaltered. Principally, numerous and more complex PV- and CB-ir Ch-terminals, as well as dense PV-ir basket formations, appeared in some hippocampal segments, whereas in other regions there was a lack of labelled elements. These changes varied considerably not only between different patients, but also within different hippocampal fields in a given patient. In general, the changes were not correlated with the clinical characteristics or degree of histopathological alterations observed in the patients, such as granular cell dispersion, neuron loss and proliferation of mossy fibres. However, some surviving neurons in the regions adjacent to the areas of neuron loss were consistently innervated by dense basket formations and complex Ch-terminals. These results indicate that, in the human epileptic hippocampus, GABAergic circuits are more highly modified than previously thought. When considered along with other extrahippocampal alterations, we suggest that these changes are important in the pathophysiology of temporal lobe epilepsy associated with hippocampal sclerosis.