Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex

Heimann, Gabor; Canhos, Luisa L.; Frik, Jesica; Jäger, Gabriele; Lepko, Tjasa; Ninkovic, Jovica; Götz, Magdalena und Sirko, Swetlana (2017): Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex. In: Cerebral Cortex, Bd. 27, Nr. 8: S. 4213-4228

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Fakultätsübergreifende Einrichtungen: Graduate School of Systemic Neurosciences (GSN)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit ; 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften
• ISSN: 1047-3211
• Sprache: Englisch