Nature│研究揭示基因与自闭症的新联系,为拯救自闭症、恢复其社会行为带来新希望

2020-08-13 生物世界 Bio生物世界

所有的孩子都生活在同一片天空下,但不是所有的孩子脸上都洋溢着天真的笑容。

所有的孩子都生活在同一片天空下,但不是所有的孩子脸上都洋溢着天真的笑容。在人类社会中,有这么一群特殊的孩子,他们不聋,却对声音充耳不闻;他们不盲,却对周围人与物视而不见;他们不哑,却不知该如何开口说话。
他们,被称为“来自星星的孩子”。
儿童自闭症,是一类以严重孤独、缺乏情感反应、语言发育障碍、刻板重复动作等反应为特征的发育障碍疾病。患有自闭症的孩子在外表上与常人一般无二,却仿佛隔了一堵无形的墙使人无法触及他们的内心。
更令人遗憾的是,目前治疗自闭症的方法十分有限,开发自闭症治疗方法的根本挑战是病情的异质性。目前已发现一百多个基因突变赋予自闭症高风险,因此每个突变仅占一小部分病例,这些突变更是涉及突出蛋白、翻译调控、染色质修饰等等多个通路。早发现、早治疗、早干预成为唯一的选择。
近日,瑞士巴塞尔大学生物中心的研究人员在国际顶尖学术期刊 Nature 杂志上发表题为:Rescue of oxytocin response and social behaviour in a mouse model of autism 的研究论文。
该研究发现了基因与自闭症之间的一种新联系——神经胶质素-3(neuroligin-3)基因的突变可以降低催产素的作用。与此同时,研究人员还报道了一种可以使自闭症患者的社会行为正常化的治疗方法,并在动物模型上取得一定成效。
统计数据表明,自闭症患者约占人类总人口的1%。从遗传学的角度来看,有许多遗传因素与自闭症的发生发展相关,目前数百个不同的自闭症相关基因已经被确认,其中包括神经胶质素-3基因。
神经角质素-3,属于脑特定神经元膜蛋白,对突触的成熟和脑功能的正常发挥是必需的。由此看来,该基因的突变极可能导致大脑的某些功能发生紊乱。然而,此前有关神经胶质素-3基因突变与自闭症症状相关的机制研究却十分匮乏。
在这项研究中,Peter Scheiffele 教授领导的研究团队在小鼠模型中发现了神经胶质素-3与催产素信号通路之间的联系。值得注意的是,催产素是一种由神经垂体分泌的激素,它可以调节哺乳动物的社会行为,特别是社会互动。
这些小鼠模型携带有特殊的基因突变,并表现出与人类自闭症相关的典型行为。因此,这些小鼠被用作研究自闭症的模型系统,并帮助科学家认知人类自闭症。
 
研究人员发现,神经胶质素-3的基因突变破坏了小鼠大脑奖赏系统神经元中的催产素信号通路,从而减少了小鼠之间的社会互动
 
进一步研究发现,神经胶质素-3的缺失影响了这些多巴胺能神经元中蛋白质合成的平衡,从而影响了神经元对催产素的反应。
Scheiffele 教授表示,“之前虽然有人推测由催产素介导的信号通路可能在自闭症中发挥作用,但这一次,我们非常惊讶地发现,神经胶质素3的突变会损害催产素信号通路。我们成功地将自闭症的两个相关机制拼合在一起!”
除此之外,研究团队通过一种新的、高度特异性的和脑渗透的激酶抑制剂——ETC168治疗神经胶质素-3基因敲除小鼠,以此恢复催产素信号通路。研究人员发现这种治疗恢复了基因敲除老鼠的社会行为——就像它们的健康同类一样。
更重要的是,研究团队还在另一个自闭症啮齿动物模型中得到了类似的实验结果,证明这种新药物可以更广泛地应用于自闭症的治疗。
总而言之,此项研究将基因突变、催产素信号通路和自闭症拼合到一起,为我们揭示了与自闭症有关的多个因素是如何相互联系的。此外,该研究结果可能会为自闭症患者的的治疗开辟了新的途径!
论文链接:
https://www.nature.com/articles/s41586-020-2563-7

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    2022-04-21 ms5000000464171069

    到底什么时候才能出来药

    0

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    2020-11-17 liye789132251
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    2021-01-20 珙桐
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    2020-10-16 1487ca73m62暂无昵称

    真想知道什么时候才能研究出治疗药物

    0

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    2020-08-15 xiongke014
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