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

摘要

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 (Ab) 1-40 and AlCl3 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 Ab1-40 and AlCl3. 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.