Contribution of Notch/Wnt signaling modulation in reactive astrocyte reparative response after brain injury

Abstract

After a Traumatic Brain Injury (TBI), the neural network activates a reparative response seeking to restore homeostasis. Astrocyte reactivation is an essential component of this response. The injury creates a temporal microenvironment where neurogenic signaling molecules regulate cell fate decisions of neocortical neural progenitors. Likewise, astrocyte reactivation triggers a transcriptional-proliferative program where neurogenic signaling molecules play crucial roles. However, precise molecular mechanisms are context-specific and are not fully understood. Here we studied cellular and molecular aspects of reactive astrocytes response after Notch-Wnt neurogenic signaling modulation. Our results provide new evidence of cortical Notch-Wnt signaling activation after TBI. Reactive astrocytes in the core of Notch signaling showed a differential aggregated distribution. In vitro, Notch inhibition promoted a neural precursor profile and might increase the number of cells committed in a proliferative response. Finally, we found an indirect co-regulation of Wnt-Shh signaling in BHLH-Notch target genes and a Notch-supportive effect in Wnt-Shh signaling activation.