中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (12): 2112-2117.doi: 10.4103/1673-5374.262597

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

N-甲基-D-天冬氨酸受体亚基1可调控精神分裂症样小鼠海马齿状回的神经发生

  

  • 出版日期:2019-12-15 发布日期:2019-12-15
  • 基金资助:

    国家自然科学基金项目（81160169，81460214，31660270，31460255），宁夏回族自治区自然科学基金项目（2018AAC02005）

N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

Juan Ding , Chun Zhang , Yi-Wei Zhang, Quan-Rui Ma, Yin-Ming Liu, Tao Sun , Juan Liu   

  1. Ningxia Key Laboratory of Cerebrocranial Diseases, Institute of Basic Medical Sciences, School of Basic Medical Sciences, Ningxia Medical
    University, Yinchuan, Ningxia Hui Autonomous Region, China
  • Online:2019-12-15 Published:2019-12-15
  • Contact: Juan Liu, PhD, ryuken0518@163.com; Tao Sun, PhD, suntao@nxmu.edu.cn
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81160169 (to JL), 81460214 (to JL), 31660270 (to JD), 31460255 (to JD); the Natural Science Foundation of Ningxia Hui Autonomous Region of China, No. 2018AAC02005 (to JL).

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摘要：

N-甲基-D-天冬氨酸受体功能减退是精神分裂症的病理生理学研究的基础，阻断N-甲基-D-天冬氨酸受体会损害学习记忆能力，并诱导大脑发生病理形态变化，但既往研究少有关注N-甲基-D-天冬氨酸受体亚基1在精神分裂症海马神经发生中的作用。(1)实验以腹腔注射0.6mg/kgN-甲基-D-天冬氨酸受体激动剂MK-801，1次/d，连续14d诱导建立精神分裂症小鼠模型，第15天时，侧脑室注射N-甲基-D-天冬氨酸。(2)以免疫荧光染色检测海马齿状回区N-甲基-D-天冬氨酸受体亚基1以及标记新生神经元的BrdU和Ki67的阳性细胞数量。(3)结果发现，精神分裂症模型小鼠海马齿状回区N-甲基-D-天冬氨酸受体亚基1阳性细胞数量增加，而BrdU和Ki67的阳性细胞数量明显减少；而N-甲基-D-天冬氨酸则逆转上述变化。(4)实验结果表明，N-甲基-D-天冬氨酸受体亚基1可以调节精神分裂症样小鼠海马齿状回区的神经发生，支持N-甲基-D-天冬氨酸受体亚基1可能作为治疗精神分裂症治疗有希望的靶点。动物实验于2014-03-06经宁夏医科大学实验动物伦理委员会（批准号2014-014）。

orcid: 0000-0002-4104-0135(Tao Sun)
          0000-0002-2434-3513(Juan Liu)

关键词: 精神分裂症, MK-801, N-甲基-D-天冬氨酸, 神经发生, N-甲基-D-天冬氨酸受体, N-甲基-D-天冬氨酸受体亚基1, BrdU, Ki67, 海马齿状回, 海马神经发生, 神经再生

Abstract:

N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.

Key words: nerve regeneration, schizophrenia, MK-801, N-methyl-D-aspartate, neurogenesis, N-methyl-D-aspartate receptor, N-methyl-Daspartate receptor subunit 1, BrdU, Ki67, hippocampal dentate gyrus, hippocampal neurogenesis, neural regeneration