3-Mercaptopropionic Acid-Induced Repetitive Seizures Increase GluN2A Expression in Rat Hippocampus: A Potential Neuroprotective Role of Cyclopentyladenosine
3-Mercaptopropionic Acid-Induced Repetitive Seizures Increase GluN2A Expression in Rat Hippocampus: A Potential Neuroprotective Role of Cyclopentyladenosine
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DOI：
10.1007/s10571-013-9947-2
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发表时间：
2013-08-01
影响因子：
4
通讯作者：
Girardi, Elena
中科院分区：
文献类型：
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作者：
Belen Gori, Maria;Girardi, Elena
N-甲基-d-天冬氨酸受体（NMDAR）参与突触可塑性、学习、记忆和神经系统疾病如癫痫，并且是兴奋性毒性的主要介质。成熟大脑中的功能性NMDAR是由不同亚基组成的异聚体复合物：GluN 1和GluN 2。有四种不同的GluN 2亚基（A-D），它们中的每一个都决定了NMDAR的药理学和电生理学特性。GluN 1在中枢神经系统中广泛表达，而GluN 2A在海马中表达最高。腺苷是一种内源性抗惊厥药，是一种神经调质，在调节神经元活动中起关键作用，介导其对特定受体的作用，其中腺苷A（1）受体在海马中高度表达。在本工作中，在急性或重复实验模型中研究了惊厥药物3-巯基丙酸（MP）诱导癫痫发作后海马GluN 2A的表达以及单独或在MP之前给予环戊基腺苷（CPA）（CPA + MP）的影响。CPA给药1天或4天可增加MP诱发的癫痫发作阈值。一次MP给药后，免疫组化结果显示CPA和CPA + MP组CA 2/3面积增加，但Western blot结果显示CPA组和CPA + MP组GluN 2A表达无显著差异。然而，在4天内重复MP给药显示GluN 2A表达显著增加，并且在MP给药前30分钟重复CPA给药导致GluN 2A表达相对于MP治疗显著降低，恢复到对照水平。这些结果表明，GluN 2A亚基参与重复MP诱导的癫痫发作，而CPA给药显示出对它的保护作用。
The N-methyl-d-aspartate receptor (NMDAR) is involved in synaptic plasticity, learning, memory, and neurological diseases like epilepsy and it is the major mediator of excitotoxicity. Functional NMDARs in the mature brain are heteromeric complexes composed of different subunits: GluN1 and GluN2. There are four different GluN2 subunits (A-D) and each of them critically determines the pharmacological and electrophysiological properties of NMDARs. GluN1 is ubiquitously expressed in the central nervous system while the highest GluN2A expression is in the hippocampus. Adenosine, an endogenous anticonvulsant, is a neuromodulator with a critical role in the regulation of neuronal activity, mediating its effect on specific receptors, among which adenosine A(1) receptor is highly expressed in the hippocampus. In the present work hippocampal GluN2A expression after the convulsant drug 3-mercaptopropionic acid (MP) induced seizures and the effect of cyclopentyladenosine (CPA) given alone or prior to MP (CPA + MP) in an acute or repetitive experimental model was studied. CPA administered to rats for one or 4 days increases seizure threshold induced by MP. After one administration of MP, no significant difference in GluN2A expression was observed in CPA and CPA + MP by Western blot, although immunohistochemistry revealed an increase in CA2/3 area. However, repetitive MP administration during 4 days showed a significant increase of GluN2A expression, and the repetitive administration of CPA 30 min prior to MP caused a significant decrease of GluN2A expression with respect to MP treatment, returning to control levels. These results show that GluN2A subunit is involved in repetitive MP-induced seizures, while CPA administration displays a protective effect against it.