Nature Neuroscience: 脑干浅层脊髓星形胶质细胞对机械感觉超敏反应的下行调控

2021-01-03 MedSci原创 MedSci原创

星形胶质细胞位于哺乳动物脑内,是胶质细胞中体积最大的一种。在中枢神经系统中,星形胶质细胞越来越被认为是调节神经元发育和功能的关键因素。

星形胶质细胞位于哺乳动物脑内,是胶质细胞中体积最大的一种。在中枢神经系统中,星形胶质细胞越来越被认为是调节神经元发育和功能的关键因素。传统上,星形胶质细胞被认为是同质性的,但最近被认为具有区域间或区域内的异质性。

在胚胎小鼠脊髓腹角(SVH)中,星形胶质细胞在区域间被分为若干个群体,并且SVH星形胶质细胞群体在运动神经元回路的发育中起作用。然而,在成人中枢神经系统中存在区域性和功能性不同的星形胶质细胞群,重要的是,它们在基于神经的行为中的作用是完全未知的。

在这项研究中,本文探索了在星形胶质细胞中表达的基因,与成人SVH相比,星形胶质细胞的转录物在成人脊髓背角(SDH)中富集。在推测的星形胶质细胞表达基因中,我们确定转录因子hairy和split 5增强子(Hes5)是SDH中最丰富的基因。HES5是Hes基因家族的一员,属于碱性螺旋-环-螺旋转录因子。HES5在胚胎神经前体细胞中高度表达,对负向调节神经和少突胶质细胞分化至关重要。HES5在胚胎神经前体细胞中高度表达,对神经和少突胶质细胞的分化起着重要的负调控作用。HES5也在出生后和成人的大脑中表达。通过观察成人脊髓中的Hes5+细胞,本研究确定了高度局限于SDH表层的星形胶质细胞群。

由于这些表层是通过初级传入纤维接收和处理来自外周的体感输入的核心区域,本研究采用多种方法研究了Hes5+星形胶质细胞在体感信息处理和行为中的作用。这些包括体内Ca2+成像、实现细胞类型选择性基因转导的病毒载体微创显微注射、化学遗传学、条件性基因敲除和行为分析。

综上所述,本文的发现表明SDH中有一个表面层选择性Hes5+星形胶质细胞群,它作为从脑干蓝斑(LC)区域发出去甲肾上腺素能(NA能)信号的通道,以调节机械感觉行为,并为成年SDH星形胶质细胞在控制神经行为方面的异质性提供了体内证据。

Kohro, Y., Matsuda, T., Yoshihara, K. et al. Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity. Nat Neurosci 23, 1376–1387 (2020). https://doi.org/10.1038/s41593-020-00713-4

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    2021-08-29 liye789132251
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    2021-01-04 lsndxfj
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    2021-01-04 jichang
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