A8 N: Role of NG2-glia in different injury paradigms
PI: L. Dimou-Rörentrop
Despite intensive research over the past decades, we still have very limited treatment options for the insufficient regeneration capacity of the central nervous system CNS after neurotrauma. Therefore, it is vital for future clinical research to understand the cellular processes contributing to tissue recovery. Here we will revolve around the NG2-glia, also known as OPCs (oligodendrocyte progenitor cells), uniformly distributed in gray and white matter of the central nervous system (CNS) and maintained as a resident population by self- renewal in the adult brain. Our focus is to understand the role and contribution of NG2-glia in two different models of brain injury, the milder and more region-restricted stab wound injury (SWI) and the clinically more frequent blunt traumatic brain injury (TBI). We could show that acute SWI leads to a fast and heterogeneous NG2-glia response, not only with morphological changes but also with an increase in their number. Genetic ablation of reactive NG2-glia resulted into effects in brain wound closure that we are currently further analysing. We also identified a NG2-glia subset that expresses the receptor GPR17, which although not differentiating under physiological conditions, after injury reacts with immediate differentiation, suggesting that these cells represent a cell reservoir responsible for brain repair. Here, we hypothesize that reactive NG2-glia are important for the repair and wound closure after stab and traumatic brain injury and that the GPR17-protein itself as well as the GPR17+ subset of NG2-glia are necessary modulators of the outcome of brain injury. Therefore, we will take advantage of the different transgenic mouse models available in the lab, perform SWI and TBI and study the role and reaction of NG2-glia concerning early danger response, proliferation, differentiation, wound closure and regeneration after injury. We plan to identify novel signaling and molecular pathways to positively regulate the outcome after injury. By using a platform of technical approaches, innovative techniques and a variety of mouse lines to fate map NG2-glia and their subsets and modulate/deplete their responses, we intend to get insights on how to promote repair after brain injury.