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Heimann, G.* ; Lange Canhos, L. ; Frik, J. ; Jäger, G.* ; Lepko, T. ; Ninkovic, J. ; Götz, M. ; Sirko, S.

Changes in the proliferative program limit astrocyte Hhmeostasis in the aged post-traumatic murine cerebral cortex.

Cereb. Cortex 27, 1-16 (2017)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Gfap ; Shh ; Aging ; Brain Injury ; Cell Division ; Glia ; Reactive Gliosis ; Self-renewal; Neural Stem-cells; Fibrillary Acidic Protein; Central-nervous-system; Glutamine-synthetase; Alzheimers-disease; Ischemic-stroke; Aging Brain; Functional Recovery; Reactive Gliosis; Transgenic Mice

ISSN (print) / ISBN 1047-3211

e-ISSN 1460-2199

Journal Cerebral Cortex

Quellenangaben Volume: 27, Issue: 8, Pages: 1-16

Publisher Oxford University Press

Publishing Place Cary

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)