The SHH/Gli pathway is reactivated in reactive glia and drives proliferation in response to neurodegeneration-induced lesions.
The SHH/Gli pathway is reactivated in reactive glia and drives proliferation in response to neurodegeneration-induced lesions.
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DOI：
10.1002/glia.22702
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发表时间：
2014-10
期刊：
影响因子：
6.2
通讯作者：
Hambardzumyan, Dolores
中科院分区：
文献类型：
--
作者：
Pitter, Kenneth L.;Tamagno, Ilaria;Feng, Xi;Ghosal, Kaushik;Amankulor, Nduka;Holland, Eric C.;Hambardzumyan, Dolores
为了应对神经变性，成年哺乳动物大脑激活细胞级联反应，导致反应性星形胶质细胞增生和小胶质细胞增生。星形胶质细胞变得活跃的机制以及它们响应神经变性而激活的生理后果是复杂的。虽然星形胶质细胞的激活和增殖已被证明发生在大量神经元细胞死亡期间，但这两个事件之间的功能关系尚未明确阐明。在这里，我们发现，为了响应红藻氨酸（KA）诱导的神经变性，反应性星形胶质细胞中的有丝分裂原声刺猬（SHH）上调。 SHH 活性在第 7 天达到峰值，并伴随着多种细胞类型中 Gli 活性的增加和增殖的增加。为了确定 KA 损伤后 SHH-Gli 信号传导的功能作用，我们使用药理学方法证明星形胶质细胞分泌的 SHH 驱动星形胶质细胞和小胶质细胞的激活和增殖。 SHH-Gli 信号传导在 KA 诱导的病变中的后果似乎与神经退行性变的严重程度无关。
In response to neurodegeneration, the adult mammalian brain activates a cellular cascade that results in reactive astro- and microgliosis. The mechanism through which astrocytes become reactive and the physiological consequences of their activation in response to neurodegeneration is complex. While the activation and proliferation of astrocytes has been shown to occur during massive neuronal cell death, the functional relationship between these two events has not been clearly elucidated. Here we show that in response to Kainic acid- (KA) induced neurodegeneration, the mitogen sonic hedgehog (SHH) is upregulated in reactive astrocytes. SHH activity peaks at 7 days and is accompanied by increased Gli activity and elevated proliferation in several cell types. To determine the functional role of SHH-Gli signaling following KA lesions, we used a pharmacological approach to show that SHH secreted by astrocytes drives the activation and proliferation of astrocytes and microglia. The consequences of SHH-Gli signaling in KA-induced lesions appear to be independent of the severity of neurodegeneration.
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影响因子：
6.2
作者：
Cui, Min;Huang, Yunlong;Tian, Changhai;Zhao, Yong;Zheng, Jialin
通讯作者：
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影响因子：
3.4
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影响因子：
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作者：
Amankulor, Nduka M.;Hambardzumyan, Dolores;Holland, Eric C.
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