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Science:爆出逆天黑科技!“咻”一束光治疗脑疾病

2018-02-10 小通 生物通

研究人员证实,确实可以通过控制参与记忆形成的一组神经元来修改与恐惧有关的行为。


研究人员证实,确实可以通过控制参与记忆形成的一组神经元来修改与恐惧有关的行为。


示意图显示近红外光如何通过脑组织并利用纳米颗粒激活神经元

十多年前光遗传学的出现,立即席卷了神经科学领域,迅速成为许多神经科学家们的首选方法。研究人员通过使用光选择性地控制活体动物脑中神经元上的离子通道,就可以实时看到特定的神经回路如何改变了动物的行为。自那以后,科学家们利用这项技术研究了从果蝇到猴子等各种物种的脑回路和功能,甚至在一个临床试验中对这种方法进行测试,恢复罕见遗传疾病患者的视力。

而今天(美国时间2月8日),最新一项光遗传学的研究成果指出,现在科学家们成功地在小鼠身上使用了基于纳米粒子的光遗传学,令这一研究领域再迈出了重要的一步,开启了未来非侵入性治疗大脑疾病的大门。

这一研究成果公布在Science杂志上,同期Science杂志也公布了另外一项重要的神经科学研究成果。

不一样的选择

日本RIKEN脑科学研究所的神经科学家Thomas  McHugh指出:“光遗传学(Optogenetics)彻底改变了我们探索脑回路的神经科学实验方式。”但是,这种技术目前需要一种永久植入的纤维,因此在过去的几年中,研究人员希望能开发出以较少侵入的方式刺激大脑的方法。许多小组尝试利用磁场,电流和声音达到这一目的。

McHugh和他的同事们决定尝试另一种方法:他们选择了近红外光,这是一种比通常用于光遗传学的蓝绿光更容易穿透组织的光源。

“这种优势在于其是一种以化学为基础的方法,我们可以利用近红外光的能量穿透组织,但是沿用的是过去十年中研发出现有工具箱中的可见光光学通道,”McHugh说。

最新这项研究则是由McHugh实验室的博士后Shuo  Chen(他在获得博士学位后从化学转向神经科学)原创性发现的,“我利用光遗传学来研究下丘脑核到海马的投射,那时候,我的问题在于,我们能不能以非侵入的方式对位于大脑深处的神经回路进行这种操纵,”Chen回忆说。

因此,Chen等人设计了一种利用纳米颗粒进行光遗传刺激的新方法,其中纳米颗粒可以将组织穿透的近红外光转换成蓝光和绿光发射(这个过程被称为upconversion,上转换,生物通译)。研究人员通过两次直接注射到大脑区域,一次是携带光门控离子通道,也称为channelrhodopsin的病毒载体,另一个携带upconversion纳米颗粒。

控制记忆神经元,修改行为

首先,研究小组从小鼠的腹侧被盖区(VTA)开始测试这种技术,这个区域深入大脑,有大量的多巴胺能神经元。在麻醉小鼠体内注射病毒载体和纳米颗粒后,研究人员在动物头部上方照射红外光,发现它们能够通过激活VTA中的神经元来刺激多巴胺释放。  Chen说:“当我们在VTA上看到来自这些纳米粒子的蓝光时,我就知道这种技术应该起作用了。这真是令人激动。”

此后,chen和他的同事在小鼠海马中进行了一系列的实验。最终,研究人员证实,确实可以通过控制参与记忆形成的一组神经元来修改与恐惧有关的行为。

光遗传学先驱Karl Deisseroth表示:“这是一篇非常好的论文,是无创靶向神经调节研究的重要一步。”

但是,目前这一技术还存在一些局限性。其中一个主要问题是upconversion的效率:纳米颗粒只能将接收到的近红外光的2.5%转换为蓝光。因此驱动这些微粒所需的能量将很难用微型无线供电的LED来实现(目前,光源不是无线的)。另外,如果要实现进入大型模式生物深层大脑结构,同时无显著加热,这个所需的能量将是难以置信的挑战。

另外汉堡大学的Wolfgang Parak也指出,另一个潜在的问题是纳米粒子如何应对人脑的可塑性。“所有细胞都喜欢吸入纳米粒子。 。  。所以粒子的位置可能随着时间的推移而发生改变。”

走向无创DBS

尽管存在挑战,基于纳米粒子的光遗传学确实令非侵入式深部脑刺激(DBS)治疗成为可能。

目前,DBS采用的是类似起博器的装置来刺激大脑,并且几十年来已经用于治疗一些神经疾病,包括帕金森病和癫痫。虽然用这种方法治疗的患者超过10万人,但是与传统的光遗传学相比,它有一个缺点,关键部件(电极和脉冲发生器)需要手术植入大脑。

多伦多大学的神经外科医生Andres  Lozano教授说:“现在这项研究提出了一个完整的菜单,可以用来激活大脑深处的组织。有大量的替代脑组织穿透技术,可以在没有永久植入硬件的前提下接近和操纵脑回路的活动。”

另外,Lozano也提出,许多这些新技术需要以某种方式转化大脑,例如基于upconversion的光遗传学,这需要将携带编码光敏离子通道基因的纳米颗粒或病毒注入大脑。另外,使这些技术起作用的程序也是侵入式的,通常需要直接注射到大脑中。但是,未来有一天也许可以通过另外的新方法,打开大脑区域的血脑屏障,比如超声波。Chen也表示,“我们正在努力发展纳米粒子,让它们穿越血脑屏障。”

为了达到治疗目的,这些非侵入性DBS都还需要进行更多的安全性和实用性的检测,因为与啮齿动物的小鼠相比,人类大脑的尺寸要大得多。

目前,这一研究团队正在努力提高纳米粒子的upconversion效率等,希望能来进一步完善其技术,并最终扩大到更大的动物,如大鼠和非人灵长类动物。

原始出处:

Shuo Chen1,et al.Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics.Science  09 Feb 2018: Vol. 359, Issue 6376, pp. 679-684 DOI: 10.1126/science.aaq1144

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    2018-07-29 hyf028
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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Sat Feb 10 07:40:34 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286678, encodeId=c2fc2866e866, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Feb 10 06:46:27 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286670, encodeId=2e882866e009, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, 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    2018-03-18 chenweiting

    现在科技太发达

    0

  4. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-17 1391e9f2a7m

    好好学习天天向上

    0

  5. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-11 jichang
  6. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-11 jyzxjiangqin

    逆天黑科技治疗脑疾病.

    0

  7. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Sun Feb 11 07:07:57 CST 2018, time=2018-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286784, encodeId=927b286e8441, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6132238020, createdName=1213a233m65暂无昵称, createdTime=Sat Feb 10 11:40:00 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286706, encodeId=8bb1286e06c9, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-10 1213a233m65暂无昵称

    不错

    0

  8. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Sun Feb 11 07:07:57 CST 2018, time=2018-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286784, encodeId=927b286e8441, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6132238020, createdName=1213a233m65暂无昵称, createdTime=Sat Feb 10 11:40:00 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286706, encodeId=8bb1286e06c9, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Sat Feb 10 07:40:34 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286678, encodeId=c2fc2866e866, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Feb 10 06:46:27 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286670, encodeId=2e882866e009, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-10 神功盖世

    0

  9. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Sun Feb 11 07:07:57 CST 2018, time=2018-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286784, encodeId=927b286e8441, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6132238020, createdName=1213a233m65暂无昵称, createdTime=Sat Feb 10 11:40:00 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286706, encodeId=8bb1286e06c9, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-10 yjs木玉

    好好好好好好好好

    0

  10. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Sun Feb 11 07:07:57 CST 2018, time=2018-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286784, encodeId=927b286e8441, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6132238020, createdName=1213a233m65暂无昵称, createdTime=Sat Feb 10 11:40:00 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286706, encodeId=8bb1286e06c9, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Sat Feb 10 06:31:20 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-10 121832a9m88暂无昵称

    学习了

    0

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Neuron :研究揭示脑部疾病治疗新靶点!确定了保护神经功能的新目标

OHSU Vollum研究所的科学家已经发现了一种在神经系统内传递信号的神经细胞线状部分的轴突变性中发挥关键作用的酶。所有神经退行性疾病都发生轴突损失,因此这一发现可以为治疗或预防广泛的脑部疾病开辟新的途径。

揭秘3D打印技术如何改善人类健康?

本文中,小编整理了近年来相关的研究报道,共同解读科学家如何利用3D打印技术来改善人类健康! 【1】3D打印卵巢具有生育能力 想一想3D打印的皮肤、耳朵、骨支架和心脏瓣膜,3D打印的爱好者会说,这种技术有产生医学革命的潜质。如今,由凝胶制成的人工卵巢能够使老鼠受孕并产下健康的后代。研究人员表示,这种工程化的卵巢总有一天能够帮助因放疗或化疗导致不育的癌症幸存者恢复生育能力。 并未参与该项

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