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NR2B 型 NMDA 受体表达及其与阿尔茨海默病样大鼠海马细胞凋亡的关系。

NR2B-containing NMDA receptors expression and their relationship to apoptosis in hippocampus of Alzheimer's disease-like rats.

机构信息

Jiangsu Province Key Laboratory of Brain Disease Bioinformation, Xuzhou, 221002, China.

出版信息

Neurochem Res. 2012 Jul;37(7):1420-7. doi: 10.1007/s11064-012-0726-0. Epub 2012 Feb 23.

Abstract

Although studies have shown that excitotoxicity mediated by N-methyl-D-aspartate receptors (NMDARs, NR) plays a prominent role in Alzheimer's disease (AD), the precise expression patterns of NMDARs and their relationship to apoptosis in AD have not been clearly established. In this study, we used Abeta (Aβ) 1-40 and AlCl(3) to establish AD rat model. The behavioral changes were detected by morris water maze and step-down test. The hippocampal amyloid deposition and pathological changes were determined by congo red and hematoxylin-eosin staining. Immunohistochemistry was used to detect expression of NR1, NR2A and NR2B, and TUNEL staining was used to detect apoptosis. Results showed that water maze testing escape latency of AD-like rats was prolonged significantly. Reaction time, basal number of errors, and number of errors of step-down test were increased significantly; latency period of step-down test was shortened significantly in AD-like rats. Amyloid substance deposition and obvious damage changes could be seen in hippocampus of AD-like rats. These results suggested that AD rat model could be successfully established by Aβ1-40 and AlCl(3). Results also showed that expression of NR1 and NR2B were significantly increased, but expression of NR2A had no significant change, in AD-like rat hippocampus. Meanwhile, apoptotic cells were significantly increased in AD-like rat hippocampus, especially in CA1 subfield and followed by dentate gyrus and CA3 subfield. These results implied that NR2B-, not NR2A-, containing NMDARs showed pathological high expression in AD-like rat hippocampus. This pathological high expression with apoptosis and selective vulnerability of hippocampus might be exist a specific relationship.

摘要

尽管研究表明,N-甲基-D-天冬氨酸受体(NMDARs,NR)介导的兴奋性毒性在阿尔茨海默病(AD)中起着重要作用,但 NMDAR 的精确表达模式及其与 AD 中细胞凋亡的关系尚未明确。在本研究中,我们使用 Abeta(Aβ)1-40 和 AlCl3 建立 AD 大鼠模型。通过 Morris 水迷宫和跳台试验检测行为变化。通过刚果红和苏木精-伊红染色检测海马淀粉样沉积和病理变化。免疫组织化学检测 NR1、NR2A 和 NR2B 的表达,TUNEL 染色检测细胞凋亡。结果表明,AD 样大鼠的水迷宫测试逃避潜伏期明显延长。反应时间、基础错误数和跳台试验错误数明显增加;AD 样大鼠的跳台试验潜伏期明显缩短。AD 样大鼠海马可见淀粉样物质沉积和明显的损伤变化。这些结果表明,Aβ1-40 和 AlCl3 可成功建立 AD 大鼠模型。结果还表明,AD 样大鼠海马中 NR1 和 NR2B 的表达明显增加,而 NR2A 的表达没有明显变化。同时,AD 样大鼠海马中凋亡细胞明显增加,特别是 CA1 区,其次是齿状回和 CA3 区。这些结果提示,AD 样大鼠海马中 NR2B-NMDAR 而非 NR2A-NMDAR 呈现病理性高表达。这种病理性高表达与凋亡和海马的选择性易损性之间可能存在特定的关系。

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