Wnt/β-catenin信号参与慢性痛引起的小鼠海马神经元发生减少  

Involvement of Wnt/β-catenin signaling in the chronic pain induced impairment of hippocampal neurogenesis

作　　者：赵又谊 张力[2] 杨吉平 王莉颖[2] 古雪[3] 刘新禹 王亚周[2] 武胜昔[2] 

机构地区：[1]成都医学院基础医学院,成都610500 [2]第四军医大学基础部神经生物学教研室,西安710032 [3]川北医学院附属医院感染科,南充637000

出　　处：《神经解剖学杂志》2017年第6期652-658,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81371240;81571224);科技部重点领域创新团队计划(2014RA4029)

摘　　要：目的:研究小鼠慢性痛模型中海马神经元发生减弱的现象,并从Wnt/β-catenin信号的角度探索相关机制,以及过表达β-catenin对慢性痛小鼠学习记忆能力的影响。方法:采用选择性坐骨神经损伤(spared nerve injury,SNI)模型,利用Brd U/DCX免疫荧光双标研究神经元发生;采用Wnt信号报告基因Topgal小鼠研究Wnt信号的改变;利用条件性过表达β-catenin的Nestin-Cre ER:β-catenin EX3^(loxp/+)小鼠研究过度激活Wnt信号对慢性痛小鼠海马神经元发生及学习记忆的影响;利用Morris水迷宫评估小鼠的空间学习记忆能力。结果:SNI后小鼠的机械和热痛阈显著下降,持续至少3周。Brd U/DCX免疫荧光双标显示SNI小鼠海马神经元发生明显减弱。Wnt信号报告基因β-gal在海马神经干细胞的表达降低。在SNI小鼠的成年神经干细胞中过表达β-catenin可显著促进海马神经元发生,并增强小鼠的空间记忆能力。结论:Wnt/β-catenin信号参与介导慢性痛引起的海马神经元发生减弱,增强Wnt信号可改善SNI小鼠海马的神经元发生及其学习记忆能力。Objective： To investigate the effects of chronic pain on hippocampal neurogenesis, explore the underly- ing mechanism through the point of Wnt/β-catenin signaling, and evaluate the effects of enhancing hippocampal neuro- genesis on the learning and memory of mice suffered from chronic pain. Methods： Chronic pain was modeled by spared nerve injury （SNI）. Neurogenesis was assessed by double-immunostaining of BrdU/DCX. Change of Wnt signaling was read out by Wnt signaling reporting transgenic mouse line Topgal mice. Nestin-CreER： β-eateninEX3lloxp/＋ mice were adopted to evaluate the effects of over-expressing β-catenin on neurogenesis and learning and memory. Spatial memory was examined by Morris water maze test. Results： SNI induces significant decrease of mechanical and thermal thresh- olds which persists for at least 3 weeks. BrdU/DCX double-immunostaining showed that the number of new-born neurons was significantly decreased in the hippocampus of mice suffered from chronic pain. The expression of Wnt signalingreporter gene,β-gal, was lowered in SNI mice. Over-expressing β-catenin in the adult neural progenitor cells of SNI mice significantly promoted neurogenesis and the learning ability of mice. Conclusion： Wnt/β-catenin signaling is involved in the chronic pain associated decrease of hippocampal neurogenesis and impairment of learning and memory.

关 键 词：慢性痛 神经元发生 海马 Wnt/β-catenin信号 学习记忆 小鼠 

分 类 号：R402[医药卫生—临床医学]