Physiological Genomics, Biomedical Center, Ludwig-Maximilians-University Munich, 82152 Planegg, Germany.
Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany.
Cereb Cortex. 2017 Aug 1;27(8):4213-4228. doi: 10.1093/cercor/bhx112.
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.
衰老会导致创伤性脑损伤后的不良后果。然而，这些缺陷的潜在机制尚不清楚。在这项研究中，我们发现，衰老的创伤性大脑皮质中的星形胶质细胞增殖反应明显减弱，导致半影区中的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，它们的增殖减少是由于与年龄相关的分裂模式转变，细胞周期再进入减少，而不是细胞周期长度的变化。值得注意的是，体内和体外的反应性星形胶质细胞对增加其增殖的刺激变得不敏感，例如 Sonic hedgehog 信号。这些数据首次表明，反应性星形胶质细胞增殖程序中依赖于年龄的、很可能是内在的变化，导致其对创伤性损伤的增殖反应严重受阻，从而影响星形胶质细胞的稳态。
