Valcárcel-Martín, R. 1, 2 , Martín-Suárez, S. 1, 2 , Sierra, A. 1, 2, 3 & Encinas, J. M. 1, 2, 3
1 Achucarro Basque Center for Neuroscience
2 University of the Basque Country (UPV/EHU)
3 Ikerbasque, the Basque Science Foundation
Radial neural stem cells (rNSCs) persist in the hippocampus of most mammals and are able to generate neurons through adulthood, a process known as adult neurogenesis. Adult hippocampal neurogenesis is important for spatial memory, pattern separation and the responses to fear, stress and anxiety. rNSCs are mostly quiescent but once they are activated, they generate neuronal precursors through several rounds of asymmetric division and then differentiate into astrocytes, losing their stem cell capabilities. We have recently discovered that after seizures rNSCs become reactive, entering symmetric division and differentiating into reactive astrocytes at the expense of their neurogenic potential.
We now hypothesize that this reaction can be a common response of rNSCs to injury. Using a model of stab wound targeting the dentate gyrus, we have found that rNSCs also become reactive and convert into reactive astrocytes in a similar manner to the situation observed after seizures. We are now exploring the long-term consequences for the neurogenic niche of rNSCs becoming reactive in this injury model. Using transgenic mice in which rNSCs can be visualized, we are investigating whether the rNSC population becomes depleted and as a consequence neurogenesis becomes chronically impaired. The loss of neurogenesis might be detrimental at two levels: impairment of the specific functions related to this process and the impossibility to regenerate the neuronal loss induced by the injury.