Abstract
SummaryRetinal ganglion cells (RGCs) do not normally regenerate axons upon optic nerve injury. However, inflammatory stimulation (IS) significantly enables axon growth in the injured optic nerve. Here, we demonstrate that optic nerve crush strongly induces inhibitory phosphorylation of GSK3α and GSK3β in RGCs. To investigate the role of GSK3 in this context we tested IS induced regeneration and neuroprotection in conditional GSK3α and GSK3β knockout mice (GSK3α‐/‐, GSK3β‐/‐) as well as GSK3αS/A and GSK3βS/A mice expressing resistant GSK3 isoforms to this inhibitory phosphorylation. In contrast to GSK3α‐/‐, GSK3β‐/‐ markedly potentiated IS induced optic nerve regeneration. On the contrary, IS mediated regeneration was significantly reduced in GSK3S/A mice. These findings suggest that active GSK3 intrinsically limits the outcome of CNS axon regeneration. Thus, treatments activating the intrinsic growth state combined with GSK3β inhibition might be suitable to further improve the regenerative outcome after CNS injury.
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