Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin
Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin
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DOI：
10.1016/s0306-4522(00)00017-8
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发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Fritschy, JM
中科院分区：
文献类型：
--
作者：
Bouilleret, V;Schwaller, B;Fritschy, JM
使用内侧颞叶癫痫的红藻氨酸模型，在单敲除和双敲除小鼠中评估了钙结合蛋白小清蛋白、钙结合蛋白和钙结合蛋白 D-28k 在癫痫发生和海马结构长期癫痫相关改变中的功能作用。使用 GABA 能中间神经元的各种标记物（GABA 转运蛋白 1 型、GABA(A) 受体 α 1 亚基、钙结合蛋白、钙结合蛋白 D-28k、生长抑素和神经肽 Y）在注射后 1 天、30 天和 4 个月评估单侧海马内注射红藻氨酸的效果。与野生型小鼠相比，小清蛋白缺陷型、小清蛋白/钙结合蛋白缺陷型和小清蛋白/钙结合蛋白缺陷型小鼠的海马结构的细胞结构以及中间神经元的数量、分布或形态没有差异。同样，突变小鼠并不更容易受到急性红藻氨酸诱导的兴奋性毒性或复发性局灶性癫痫发作的长期影响，并且表现出与野生型动物相同的神经化学改变模式（例如，颗粒细胞中神经肽Y的双侧诱导）和形态发生变化（齿状回颗粒细胞的增大和分散）。中间神经元的定量显示基因型之间的神经元脆弱性没有显着差异。这些结果表明这里研究的钙结合蛋白对于确定中间神经元的神经化学表型不是必需的。此外，在该模型中它们不能防止红藻氨酸诱导的兴奋性毒性，并且似乎不能调节海马体兴奋性的总体水平。最后，癫痫发作引起的颗粒细胞基因表达的变化，通常表达高水平的钙结合蛋白，显然不受所分析的基因删除的影响。 (C) 2000 国际广播组织。由爱思唯尔科学领导出版。
The functional role of the calcium-binding proteins parvalbumin, calretinin, and calbindin D-28k for epileptogenesis and long-term seizure-related alterations of the hippocampal formation was assessed in single- and double-knockout mice, using a kainate model of mesial temporal lobe epilepsy. The effects of a unilateral intrahippocampal injection of kainic acid were assessed at one day, 30 days, and four months post-injection, using various markers of GABAergic interneurons (GABA-transporter type 1, GABA(A)-receptor alpha 1 subunit, calretinin, calbindin D-28k, somatostatin, and neuropeptide Y). Parvalbumin-deficient, parvalbumin/calbindin-deficient, and parvalbumin/calretinin-deficient mice exhibited no difference in cytoarchitecture of the hippocampal formation and in the number, distribution, or morphology of interneurons compared to wild-type mice. Likewise, mutant mice were not more vulnerable to acute kainate-induced excitotoxicity or to long-term effects of recurrent focal seizures, and exhibited the same pattern of neurochemical alterations (e.g., bilateral induction of neuropeptide Y in granule cells) and morphogenic changes (enlargement and dispersion of dentate gyrus granule cells) as wild-type animals. Quantification of interneurons revealed no significant difference in neuronal vulnerability among the genotypes.These results indicate that the calcium-binding proteins investigated here are not essential for determining the neurochemical phenotype of interneurons. Furthermore, they are not protective against kainate-induced excitotoxicity in this model, and do not appear to modulate the overall level of excitability of the hippocampus. Finally, seizure-induced changes in gene expression in granule cells, which normally express high levels of calcium-binding proteins, apparently were not affected by the gene deletions analysed. (C) 2000 IBRO. Published by Elsevier Science Led.