Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex
Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex
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DOI：
10.1093/cercor/bhx112
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发表时间：
2017-08-01
期刊：
影响因子：
3.7
通讯作者：
Sirko, Swetlana
中科院分区：
文献类型：
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作者：
Heimann, Gabor;Canhos, Luisa L.;Sirko, Swetlana
衰老会导致创伤性脑损伤后的不良后果。然而，这些缺陷背后的机制尚不清楚。在这项研究中，我们发现老年创伤后大脑皮层星形胶质细胞的增殖反应显著降低，导致半影区星形胶质细胞数量减少。此外，体外反应性星形胶质细胞的实验表明，它们增殖的减弱是由于与年龄相关的分裂模式的切换，减少了细胞周期的重新进入，而不是细胞周期长度的变化。值得注意的是，体内和体外反应性星形胶质细胞在老化过程中对促进其增殖的刺激变得不耐受，例如Sonic Hedgehog信号。这些数据首次表明，反应性星形胶质细胞的增殖程序中与年龄相关的内在变化导致其对创伤的增殖反应严重受阻，从而影响星形胶质细胞的动态平衡。
Aging leads to adverse outcomes after traumatic brain injury. The mechanisms underlying these defects, however, are not yet clear. In this study, we found that astrocytes in the aged post-traumatic cerebral cortex develop a significantly reduced proliferative response, resulting in reduced astrocyte numbers in the penumbra. Moreover, experiments of reactive astrocytes in vitro reveal that their diminished proliferation is due to an age-related switch in the division mode with reduced cell-cycle re-entry rather than changes in cell-cycle length. Notably, reactive astrocytes in vivo and in vitro become refractory to stimuli increasing their proliferation during aging, such as Sonic hedgehog signaling. These data demonstrate for the first time that age-dependent, most likely intrinsic changes in the proliferative program of reactive astrocytes result in their severely hampered proliferative response to traumatic injury thereby affecting astrocyte homeostasis.