Aging Cell:布洛芬拯救衰老过程中的记忆缺失

2020-09-14 haibei MedSci原创

慢性炎症是许多神经退行性疾病的一个特征,并与年龄依赖性认知衰退有关。系统性炎症的生物标志物在认知能力下降的个体中升高,并被推测可能有助于提高发展痴呆症的风险。

慢性炎症是许多神经退行性疾病的一个特征,并与年龄依赖性认知衰退有关。系统性炎症的生物标志物在认知能力下降的个体中升高,并被推测可能有助于提高发展痴呆症的风险。

细胞衰老是一种以不可逆的细胞周期停滞为特征的状态,可由多种应激因素引发,包括端粒功能障碍、氧化应激和炎症等。衰老伴随着由多种信号通路驱动的一系列表型变化,并由一个复杂的自分泌和旁分泌强化网络维持。

衰老的特点是分泌一些促炎细胞因子、趋化因子和基质蛋白酶,通常被命名为衰老相关分泌表型(SASP),其中许多通过NF-κB调节。SASP的慢性诱导被认为是衰老过程中与年龄相关的病理和年龄相关疾病的原因,包括神经退行性疾病,如阿尔茨海默病(AD)和帕金森病(PD)。

因此,研究表明,衰老和神经退行性疾病期间大脑中的衰老细胞增加,并且通过去除衰老细胞可以改善PD、AD和tau依赖性神经退行性疾病小鼠模型的表型。然而,至今为止,体内驱动大脑细胞衰老的机制尚未阐明。

最近,研究人员在Aging Cell发文,其采用基因增强NF-κB活性(nfκb1-/-)的小鼠模型,研究炎症对认知能力下降的影响。该小鼠模型以低级慢性炎症和过早衰老为特征。

研究人员发现,在衰老过程中,nfkb1-/-小鼠表现出早期的记忆力下降,并伴随着神经炎症的增强,海马和小脑中衰老细胞的出现频率增加。nfkb1-/-小鼠海马体外的电生理测量也显示了伽马频率振荡的缺陷,这可以表征其记忆能力的下降。

重要的是,用非甾体类抗炎药(NASID)布洛芬治疗可减少神经炎症和衰老细胞负担,从而显著改善认知功能和伽马频率振荡。

研究人员首先使用强制交替臂Y-maze测试评估小鼠短期记忆和空间学习能力。与nfkb1-/-小鼠相反,野生型小鼠表现出对探索新颖手臂的偏好。用布洛芬治疗2个月,增加了nfkb1-/-小鼠对新颖手臂的初级探索频率,并显著缩短了新颖手臂进入的潜伏期,这种对新颖手臂的偏好在测试的前2分钟内的探索过程中由较高的交替指数表示。Nfkb1-/-表现出较低的交替指数,而布洛芬可解救这种情况。

为了评估短期和长期记忆,研究人员还使用了巴恩斯迷宫测试,该测试通过训练动物在周围墙壁上附着的视觉线索的帮助下找到一个逃生箱来测量空间记忆。研究人员发现,年轻的野生型小鼠比nfkb1-/-小鼠更频繁地探索目标洞(高达25%)。用布洛芬治疗2个月并没有显著改变搜索分布。然而,8个月的布洛芬治疗显著改善了18月龄nfkb1-/-的短期和长期记忆。

巴恩斯迷宫测试允许研究人员更详细地分析组间的搜索策略。有3种不同的搜索策略可以呈现:(a)直接搜索(小鼠直接搜索目标孔或相邻孔),(b)序列搜索(小鼠在找到目标孔之前至少搜索2个序列孔),(c)混合搜索(小鼠随机搜索)。混合搜索策略一般是认知障碍比较严重的指标。研究人员发现,在18个月龄时,37%的nfkb1-/-小鼠在短期记忆测试中应用混合/随机搜索策略,而野生型小鼠的比例为8%。重要的是,布洛芬治疗后,nfkb1-/-小鼠应用这种搜索策略的比例降低到12.5%。在长期记忆测试中也得到了类似的结果 。

这些数据支持慢性炎症是在衰老过程中观察到的认知能力下降的一个致病因素的假设。

 

原始出处:

Edward Fielder et al. Anti‐inflammatory treatment rescues memory deficits during aging in nfkb1-/- mice. Aging Cell (2020). DOI: https://doi.org/10.1111/acel.13188

 

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    2020-12-26 爆笑小医
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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200903/79d0f015e6084e5ca462828ca002414e/27d5d6b264cb4eeebf7092dc1fb8eae8.jpg, createdBy=22155415237, createdName=ms7000000139248197, createdTime=Mon Sep 14 07:44:13 CST 2020, time=2020-09-14, status=1, ipAttribution=)]
    2020-09-16 14818eb4m67暂无昵称

    学习

    0

  4. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200903/79d0f015e6084e5ca462828ca002414e/27d5d6b264cb4eeebf7092dc1fb8eae8.jpg, createdBy=22155415237, createdName=ms7000000139248197, createdTime=Mon Sep 14 07:44:13 CST 2020, time=2020-09-14, status=1, ipAttribution=)]
    2020-09-15 ms7000000675961159

    学习了

    0

  5. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200903/79d0f015e6084e5ca462828ca002414e/27d5d6b264cb4eeebf7092dc1fb8eae8.jpg, createdBy=22155415237, createdName=ms7000000139248197, createdTime=Mon Sep 14 07:44:13 CST 2020, time=2020-09-14, status=1, ipAttribution=)]
    2020-09-14 zhq379

    提高新的认识

    0

  6. 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topicName=null, topicId=null, topicList=[TopicDto(id=48420, encryptionId=197c484205b, topicName=布洛芬), TopicDto(id=74364, encryptionId=71b2e4364f5, topicName=神经炎症), TopicDto(id=103906, encryptionId=36d6103906b1, topicName=衰老细胞负担)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211019/df01a4bfb64246379ddfef3370d04115/e1274c8eb5e440918f56f83bcfea9031.jpg, createdBy=3a345397082, createdName=Jessica, createdTime=Mon Sep 14 22:49:23 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885183, encodeId=b907885183cc, content=<a href='/topic/show?id=197c484205b' target=_blank style='color:#2F92EE;'>#布洛芬#</a>能拯救<a href='/topic/show?id=4c239032154' target=_blank style='color:#2F92EE;'>#衰老#</a>过程中的<a href='/topic/show?id=76869131495' target=_blank style='color:#2F92EE;'>#记忆#</a>缺失,令人不太相信哦,如果真如此,真是<a href='/topic/show?id=9efb80281aa' target=_blank style='color:#2F92EE;'>#老药新用#</a>,创造了历史, beContent=null, 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200903/79d0f015e6084e5ca462828ca002414e/27d5d6b264cb4eeebf7092dc1fb8eae8.jpg, createdBy=22155415237, createdName=ms7000000139248197, createdTime=Mon Sep 14 07:44:13 CST 2020, time=2020-09-14, status=1, ipAttribution=)]
    2020-09-14 Jessica

    用非甾体类抗炎药(NASID)#布洛芬#治疗可减少#神经炎症##衰老细胞负担#,从而显著改善认知功能和伽马频率振荡。布洛芬竟然还有这个神奇的功能!

    0

  7. 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topicName=null, topicId=null, topicList=[TopicDto(id=48420, encryptionId=197c484205b, topicName=布洛芬), TopicDto(id=74364, encryptionId=71b2e4364f5, topicName=神经炎症), TopicDto(id=103906, encryptionId=36d6103906b1, topicName=衰老细胞负担)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211019/df01a4bfb64246379ddfef3370d04115/e1274c8eb5e440918f56f83bcfea9031.jpg, createdBy=3a345397082, createdName=Jessica, createdTime=Mon Sep 14 22:49:23 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885183, encodeId=b907885183cc, content=<a href='/topic/show?id=197c484205b' target=_blank style='color:#2F92EE;'>#布洛芬#</a>能拯救<a href='/topic/show?id=4c239032154' target=_blank style='color:#2F92EE;'>#衰老#</a>过程中的<a href='/topic/show?id=76869131495' target=_blank style='color:#2F92EE;'>#记忆#</a>缺失,令人不太相信哦,如果真如此,真是<a href='/topic/show?id=9efb80281aa' target=_blank style='color:#2F92EE;'>#老药新用#</a>,创造了历史, beContent=null, 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200903/79d0f015e6084e5ca462828ca002414e/27d5d6b264cb4eeebf7092dc1fb8eae8.jpg, createdBy=22155415237, createdName=ms7000000139248197, createdTime=Mon Sep 14 07:44:13 CST 2020, time=2020-09-14, status=1, ipAttribution=)]
    2020-09-14 lovetcm

    #布洛芬#能拯救#衰老#过程中的#记忆#缺失,令人不太相信哦,如果真如此,真是#老药新用#,创造了历史

    0

  8. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200903/79d0f015e6084e5ca462828ca002414e/27d5d6b264cb4eeebf7092dc1fb8eae8.jpg, createdBy=22155415237, createdName=ms7000000139248197, createdTime=Mon Sep 14 07:44:13 CST 2020, time=2020-09-14, status=1, ipAttribution=)]
    2020-09-14 责任人

    学习

    0

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