Mol Psychiatry:实锤了!高胆碱饮食可抗击阿尔茨海默病!

2019-01-10 Ruthy 转化医学网

有学者指出,中国正逐步走进老龄化社会,退行性病变明显增多,神经变性疾病已成为四大死因之一,阿尔茨海默病(AD)则是老年人神经变性疾病的最常见类型。其中,家族性阿尔茨海默病(FAD)患者起病更早、进展迅速、病情更严重,而根治之法的问世却不知何年何月。近日,亚利桑那州立大学生命科学学院的研究人员指出,长期高胆碱饮食竟然可以有效改善FAD!而且该治疗效应还可以延续至下一代!这为神经变性疾病的表观遗传


导  读

有学者指出,中国正逐步走进老龄化社会,退行性病变明显增多,神经变性疾病已成为四大死因之一,阿尔茨海默病(AD)则是老年人神经变性疾病的最常见类型。其中,家族性阿尔茨海默病(FAD)患者起病更早、进展迅速、病情更严重,而根治之法的问世却不知何年何月。近日,亚利桑那州立大学生命科学学院的研究人员指出,长期高胆碱饮食竟然可以有效改善FAD!而且该治疗效应还可以延续至下一代!这为神经变性疾病的表观遗传学研究提供了新思路!

AD是一种起病隐匿、进行性发展的神经系统退行性疾病,多起病于老年期,潜隐起病,病程迟缓且不成逆,临床上以智能损害为主。病理改变首要为皮质满盈性萎缩,沟回增宽,脑室扩年夜,神经元年夜量削减,并可见老年斑老年斑(SP),神经原纤维结(NFT)等病变,胆碱乙酰化酶及乙酰胆碱含量显著削减,病因迄今未明。

而FAD家族往往有明确的家族史,50~70%的家族可以查到明确的基因突变。我们知道大脑一旦损伤,想要复原便难如登天,对FAD基因突变的携带者,难道痴呆之路竟是必由之路?是否有办法延缓甚至阻断AD的到来呢?

胆碱与AD/FAD

胆碱是少数能够穿过血脑屏障的物质之一。穿过此屏障后胆碱可以促进大脑记忆区细胞的生长发育,其可以进入脑细胞中,制造帮助记忆的化学物质,故而胆碱可以促进脑发育、增强记忆力。

此外,胆碱还是构成乙酰胆碱的主要成分,在神经信号的传递中起着重要作用。一旦脑内长期处于持续性低胆碱状态,会导致胆碱能神经元缺失,进而发生乙酰胆碱酶缺乏,同时导致大脑记忆区细胞发育异常,这些都是AD患者认知功能减退的元凶。也就是说,想要延缓甚至阻断AD的发展,维持脑内胆碱的正常水平至关重要。

高胆碱饮食与AD/FAD

如何维持脑内胆碱水平?既然胆碱可以通过血脑屏障,自然选择最安全的方式—饮食。研究人员对孕期已表现出AD样症状的FAD小鼠喂食高胆碱食物一段时间,他们发现实验组的母体的认知功能得到极大改善,而其子鼠不管有没有喂食高胆碱饮食,其空间记忆能力也明显优于对照组!

随后对小鼠海马组织的分析发现高胆碱饮食的小鼠亲代和子代的海马区基因表达发生了改变!海马区的发育都趋于正常!这就证实了高胆碱饮食可以诱导大脑的表观遗传改变!而且这种改变可以遗传给后代!

高胆碱饮食亲代小鼠改善空间记忆能力和淀粉样蛋白斑块水平

高胆碱饮食亲代小鼠改善AD样病理

高胆碱饮食使小鼠海马区基因表达发生改变

进一步的机理研究发现,补充胆碱可通过改变蛋氨酸循环降低脑内同型半胱氨酸的水平,而同型半胱氨酸是一种可作为强效神经毒素的氨基酸,其是AD患者神经变性和淀粉样蛋白斑块形成的关键!同时,胆碱还可以减少小胶质细胞的活化,而小胶质细胞的活化失控正是AD的重要标志之一!简而言之,足够的胆碱就可以全方位对抗AD,甚至遏制AD的发生!

这项研究提出了一种延缓甚至遏制AD发生发展的安全途径,因为胆碱是一种非常安全的药物替代物。但目前该成果只在小鼠实验中证实,因而需要更多时间和精力去获取人体临床实验的相关数据,才能真正确定胆碱在阻碍AD发生发展过程中发挥的作用。AD无论对个人还是家庭都是一场灾难,对社会也是沉重的负担,我们期待有更多好消息降临。

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    2019-01-28 kafei

    学习了谢谢

    0

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    2019-01-12 grace5704
  7. [GetPortalCommentsPageByObjectIdResponse(id=1817908, encodeId=b084181e90867, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Sat Aug 03 07:17:00 CST 2019, time=2019-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1816885, encodeId=971c181688523, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Fri Jan 18 07:17:00 CST 2019, time=2019-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1792137, encodeId=65f61e92137a1, content=<a href='/topic/show?id=696a14818df' target=_blank style='color:#2F92EE;'>#Psychiatry#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14818, encryptionId=696a14818df, topicName=Psychiatry)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c192448, createdName=diushouji, createdTime=Tue Jan 15 18:17:00 CST 2019, time=2019-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=359406, encodeId=3beb359406a6, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Mon Jan 28 07:22:34 CST 2019, time=2019-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470262, encodeId=7b5714e02625b, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Sat Jan 12 12:17:00 CST 2019, time=2019-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527406, encodeId=afa7152e40669, content=<a href='/topic/show?id=10b483495a2' target=_blank style='color:#2F92EE;'>#胆碱#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83495, encryptionId=10b483495a2, topicName=胆碱)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ce6211859522, createdName=grace5704, createdTime=Sat Jan 12 12:17:00 CST 2019, time=2019-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=357781, encodeId=052535e7813d, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Jan 10 21:28:30 CST 2019, time=2019-01-10, status=1, ipAttribution=)]
    2019-01-10 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0