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N-甲基-D-天冬氨酸受体亚基1调节精神分裂症样小鼠海马齿状回中的神经发生。

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

作者信息

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

机构信息

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.

出版信息

Neural Regen Res. 2019 Dec;14(12):2112-2117. doi: 10.4103/1673-5374.262597.

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.

摘要

N-甲基-D-天冬氨酸受体功能减退是精神分裂症病理生理学的基础。阻断N-甲基-D-天冬氨酸受体会损害学习和记忆能力,并诱发大脑的病理变化。以往的研究很少关注N-甲基-D-天冬氨酸受体亚基1(NR1)在精神分裂症海马神经发生中的作用。通过腹腔注射0.6 mg/kg MK-801建立精神分裂症小鼠模型,每天1次,共14天。在第15天,对精神分裂症小鼠进行脑室注射N-甲基-D-天冬氨酸处理。通过免疫荧光染色测量齿状回中NR1、Ki67或BrdU免疫反应性细胞的数量。我们的数据显示,与对照组相比,精神分裂症组中NR1免疫反应性细胞的数量随着BrdU和Ki67免疫反应性细胞数量的减少而增加。N-甲基-D-天冬氨酸可以逆转上述变化。这些结果表明,NR1可以调节精神分裂症小鼠海马齿状回的神经发生,支持NR1作为治疗精神分裂症的一个有前景的治疗靶点。本研究于2014年3月6日获得中国宁夏医科大学实验动物伦理委员会批准(批准号:2014-014)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/466d/6788228/f9f99cab148d/NRR-14-2112-g002.jpg

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