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NR2B-Containing NMDA Receptors Expression and Their Relationship to Apoptosis in Hippocampus of Alzheimer’s Disease-Like Rats

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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 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 Aβ1-40 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.

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Acknowledgments

This work was supported by grants from the Key Laboratory of Brain Disease Bioinformation of Jiangsu Province (No. JSBL0903), the National Natural Science Foundation of China (No. 30800309, 30800446) and the Natural Science Foundation of Jiangsu Province (No. BK2009087).

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Authors and Affiliations

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

    Zhi’an Liu & Tiejun Xu

  2. Department of Anatomy and Neurobiology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, China

    Zhi’an Liu, Chun’e Lv, Yuanjian Song & Tiejun Xu

  3. Department of Radiology, Affiliated Xijing Hospital of Fourth Military Medical University, Xi’an, 710032, China

    Weiwei Zhao

  4. Jiangsu Province Key Laboratory of Biological Cancer Therapy, Xuzhou, 221002, China

    Dongsheng Pei

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  1. Zhi’an Liu
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  2. Chun’e Lv
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  3. Weiwei Zhao
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  4. Yuanjian Song
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  5. Dongsheng Pei
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  6. Tiejun Xu
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Corresponding authors

Correspondence to Zhi’an Liu or Tiejun Xu.

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Zhi’an Liu, Chun’e Lv and Weiwei Zhao have contributed equally to this work.

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Liu, Z., Lv, C., Zhao, W. et al. NR2B-Containing NMDA Receptors Expression and Their Relationship to Apoptosis in Hippocampus of Alzheimer’s Disease-Like Rats. Neurochem Res 37, 1420–1427 (2012). https://doi.org/10.1007/s11064-012-0726-0

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  • DOI: https://doi.org/10.1007/s11064-012-0726-0

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