Astrocyte activation is suppressed in both normal and injured brain by FGF signaling
Astrocyte activation is suppressed in both normal and injured brain by FGF signaling
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DOI：
10.1073/pnas.1320401111
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发表时间：
2014-07-22
影响因子：
11.1
通讯作者：
Hebert, Jean M.
中科院分区：
文献类型：
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作者：
Kang, Wenfei;Balordi, Francesca;Hebert, Jean M.
在大脑中，星形胶质细胞是一种多功能细胞，它能对损伤做出反应并含有损伤。然而，过多或持续的反应性星形胶质细胞可能对功能恢复有害或导致慢性炎症和神经元功能障碍。因此，星形胶质细胞对损伤反应的激活可能受到严格调控。虽然已经确定了激活星形胶质细胞的因素，但是否也存在使星形胶质细胞保持非反应性或在含有损伤后重建其非反应性状态的因素尚不清楚。通过使用功能失得遗传方法，我们发现，在未受干扰的成人新皮层中，星形胶质细胞需要FGF信号来维持其非反应状态。同样，在损伤后，FGF信号传导延迟星形胶质细胞的反应并加速其失活。此外，破坏星形细胞FGF受体可减少疤痕大小，但不影响神经元存活。总的来说，本研究揭示了正常和损伤的新皮层中星形胶质细胞的激活不仅受促炎因子的调节，还受抑制激活的因子如FGFs的调节，从而提供了替代的治疗靶点。
In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss-and gain-of-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets.