5-Aza-cdR可能通过提高海马组织内NR2B磷酸化水平改善小鼠学习和记忆能力

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (8): 1091-1096.

• 研究论文 • 下一篇

5-Aza-cdR可能通过提高海马组织内NR2B磷酸化水平改善小鼠学习和记忆能力

刘晓蕾¹, 王强², 张晓璐¹, 邵国^1*, 姜树原^1,3*

包头医学院1.内蒙古自治区低氧转化医学重点实验室;2.基础医学与法医学院;3.药学院,内蒙古包头 014040

收稿日期:2021-03-01 修回日期:2021-06-20 出版日期:2021-08-05 发布日期:2021-07-21
通讯作者: *Shao_guo_China@163.com; jiang_shuyuan_800@163.com
基金资助:
国家自然科学基金(81660307,82060337);内蒙古自然科学基金(2020MS08006,2020MS08172);内蒙古自治区高等学校科研项目(NJZY17250);包头医学院科学研究基金(BYJJ-YF 201719,BYJJ-QM-2018004)

5-Aza-cdR improves learning capacity and memory through enhancing NR2B phosphorylation level in hippocampus of mice

LIU Xiao-lei¹, WANG Qiang², ZHANG Xiao-lu¹, SHAO Guo^1*, JIANG Shu-yuan^1,3*

1. Inner Mongolia Key Laboratory of Hypoxic Translational Medicine;2. School of Basic Medicine and Forensic Medicine;3. School of Pharmacy, Baotou Medical College, Baotou 014040,China

Received:2021-03-01 Revised:2021-06-20 Online:2021-08-05 Published:2021-07-21
Contact: *Shao_guo_China@163.com; jiang_shuyuan_800@163.com

摘要/Abstract

摘要： 目的研究5-氮杂-2′-脱氧胞苷(5-Aza-CdR)对小鼠在跳台实验中的学习和记忆能力及其海马组织中NR2B 1472位点的酪氨酸磷酸化(p-Y1472 NR2B)的影响。方法将小鼠随机分为对照组(control)和5-Aza-CdR处理组(5-Aza-CdR)。侧脑室内注射10 μmol/L 5-Aza-CdR,通过跳台实验检测小鼠的行为、学习和记忆能力。采用real-time PCR检测小鼠海马组织中NR2B mRNA的表达;Western blot和免疫荧光检测小鼠海马组织NR2B和磷酸化NR2B-Y1472(p-Y1472 NR2B)的表达水平。结果 5-Aza-CdR组小鼠在跳台实验中潜伏期增加,错误次数减少,学习和记忆能力明显提高(P＜0.05),同时,小鼠海马组织中NR2B mRNA和蛋白的表达水平均无明显变化,NR2B-Y1472的磷酸化水平升高(P＜0.05),CDK5活性降低(P＜0.05)。CA1区和CA3区NR2B荧光强度无差异,而CA1区p-Y1472 NR2B显著升高(P＜0.05)。结论 5-Aza-CdR对学习和记忆能力的影响可能与海马中p-Y1472 NR2B磷酸化相关。

关键词: 5-Aza-CdR, NR2B, p-Y1472 NR2B, 学习和记忆

Abstract: Objective To study the effects of 5-Aza-2′-deoxycytidine (5-Aza-CdR) on learning and memory capacity of mice by step-down test and tyrosine phosphorylation of NR2B 1472 site (p-Y1472 NR2B) in hippocampus. Methods Mice were randomly divided into control group (control) and 5-Aza-CdR treatment group (5-Aza-CdR). In the test, 5-Aza-CdR (10 μmol/L) was administered to treatment group mice via intracerebroventricular injection. The ability of learning and memory in mice was evaluated by step-down test. The mRNA level of NR2B in hippocampal tissues of mice was measured by real-time PCR. NR2B and p-Y1472 NR2B in hippocampal tissues of mice were measured by Western blot and immunofluorescence. Results In the 5-Aza-CdR treatment group, the latency period was increased, the error records were decreased, the behavioral memory was significantly improved in step-down test(P＜0.05). While the expression of NR2B mRNA and protein in the hippocampus of mice was not significantly changed, the phosphorylation of p-Y1472 NR2B was increased(P＜0.05), and CDK5 activity was decreased(P＜0.05). There was no difference in NR2B fluorescence intensity between CA1 region and CA3 region, while p-Y1472 NR2B in CA1 region was significantly increased (P＜0.05). Conclusions The effects of 5-Aza-CdR on behavioral memory ability may be related to the p-Y1472 NR2B in the hippocampus of mice.

Key words: 5-Aza-CdR, NR2B, p-Y1472 NR2B, learning and memory

中图分类号:

R338

刘晓蕾, 王强, 张晓璐, 邵国, 姜树原. 5-Aza-cdR可能通过提高海马组织内NR2B磷酸化水平改善小鼠学习和记忆能力[J]. 基础医学与临床, 2021, 41(8): 1091-1096.

LIU Xiao-lei, WANG Qiang, ZHANG Xiao-lu, SHAO Guo, JIANG Shu-yuan. 5-Aza-cdR improves learning capacity and memory through enhancing NR2B phosphorylation level in hippocampus of mice[J]. Basic & Clinical Medicine, 2021, 41(8): 1091-1096.

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5-Aza-cdR可能通过提高海马组织内NR2B磷酸化水平改善小鼠学习和记忆能力

5-Aza-cdR improves learning capacity and memory through enhancing NR2B phosphorylation level in hippocampus of mice

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