首页|雷帕霉素促进创伤后应激障碍模型小鼠恐惧记忆消退的研究

雷帕霉素促进创伤后应激障碍模型小鼠恐惧记忆消退的研究

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目的 探讨雷帕霉素通过促进自噬对创伤后应激障碍(Posttraumatic stress disorder,PTSD)模型小鼠恐惧记忆消退的影响。方法 通过条件恐惧消退训练构建创伤后应激障碍小鼠模型,蛋白印迹检测微管相关蛋白1轻链3(LC3)和Beclin-1的蛋白表达水平。免疫荧光染色检测LC3表达。通过脑区立体定位将雷帕霉素注射到小鼠海马区,条件恐惧记忆消退训练评估其对小鼠恐惧记忆消退的影响。结果 与未训练组相比,恐惧记忆消退训练后自噬相关蛋白Beclin-1和LC3-Ⅱ的蛋白表达显著升高(P<0。01)。雷帕霉素(10μmol·L-1)处理HT22细胞后,细胞质中LC3的荧光数量增加。海马区给予雷帕霉素促进恐惧消退训练(P<0。05),并降低消退训练后24 h的恐惧记忆水平(P<0。05)。结论 本研究发现雷帕霉素可促进恐惧记忆消退,降低恐惧记忆水平,其机制可能与自噬水平增加有关。本研究结果为PTSD的药物研发提供了理论基础。
Study on Rapamycin Facilitating Fear Memory Extinction in A PTSD Mouse Model
OBJECTIVE To investigate the effect of rapamycin on fear memory extinctionin PTSD model mice by promoting autophagy.METHODS Amouse model of post-traumatic stress disorder(PTSD)was established through conditioned fear extinction training.Subsequently,western blotting was employed to assess levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 and LC3 expression was assessed through immunofluorescence staining.Rapamycin was administered into the hippocampus of mice via stereotaxic brain injection.The impact of rapamycin on fear memory extinction was assessed through conditioned fear memory extinction training experiments.RESULTS Compared with the untrained group,the expressions of autophagy-related proteins Beclin-1 and LC3-Ⅱ significantly increased following fear memory extinction training(P<0.01).Additionally,after treatment with rapamycin(10 μmol·L-1)on HT22 cells,rapamycin enhanced the immunostaining puncta of autophagy protein LC3 and promoted fear memory extinction(P<0.05).CONCLUSION This study found that rapamycin can promote fear memory extinction and reduce fear memory levels,possibly through an increase in autophagy levels.These findings provide a theoretical basis for drug development for PTSD.

rapamycinautophagyfear memory extinctionLC3

吴宋芬、庄海才、李宽

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广东医科大学药学院,广东东莞 523000

深圳市人民医院(暨南大学第二临床医学,南方科技大学第一附属医院),广东深圳 518020

雷帕霉素 自噬 恐惧记忆消退 LC3

深圳市科创委基础研究面上项目

JCYJ20190807150005699

2024

今日药学
广东省药学会 中国药学会

今日药学

影响因子:0.413
ISSN:1674-229X
年,卷(期):2024.34(7)