Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus
Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus
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DOI：
10.1016/j.eplepsyres.2008.02.006
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发表时间：
2008-05-01
影响因子：
2.2
通讯作者：
DeLorenzo, Robert J.
中科院分区：
文献类型：
--
作者：
Carter, Dawn S.;Harrison, Anne J.;DeLorenzo, Robert J.
获得性癫痫（AE）的特征是自发性复发性癫痫发作和在损伤后存活神经元发生的长期变化，如癫痫持续状态（SE）。在AE的体内和体外模型中都观察到海马Ca2+稳态的长期改变。钙离子动态平衡的一个主要调节因子是神经元钙结合蛋白calbinin - d28k，它用于缓冲和运输Ca2+离子。本研究评价了匹罗卡品模型大鼠AE海马calbindin的表达水平。癫痫动物海马Calbindin蛋白表达减少50%以上。在校正细胞损失后，在CA1的锥体层、CA3的透明层、门、齿状回的颗粒层和分子层中观察到这种减少。此外，单个神经元中的钙结合蛋白水平也显著降低。此外，癫痫动物calbindin mRNA表达降低。时间过程研究表明，在匹罗卡品诱导的SE发作后1个月，calbindin的表达开始下降，并在SE发作后2年出现。结果表明，AE海马区calbindin基本永久性减少。海马钙结合蛋白的减少可能是癫痫发生中发生的一些可塑性变化的主要促成因素，并有助于与AE相关的Ca2+稳态的改变。(c) 2008 Elsevier B.V.版权所有
Acquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca2+ homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca2+ homeostasis is the neuronal calcium binding protein, calbindin-D28k that serves to buffer and transport Ca2+, ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and tasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca2+ homeostasis associated with AE. (c) 2008 Elsevier B.V. All rights reserved.