A new role for interferon gamma in neural stem/precursor cell dysregulation

Background: The identification of factors that compromise neurogenesis is aimed at improving stem cell-based approaches in the field of regenerative medicine. Interferon gamma (IFN gamma) is a main pro-inflammatory cytokine and up-regulated during several neurological diseases. IFN gamma is generally thought to beneficially enhance neurogenesis from fetal or adult neural stem/precursor cells (NSPCs). Results: We now provide direct evidence to the contrary that IFN gamma induces a dysfunctional stage in a substantial portion of NSPC-derived progeny in vitro characterized by simultaneous expression of glial fibrillary acid protein (GFAP) and neuronal markers, an abnormal gene expression and a functional phenotype neither typical for neurons nor for mature astrocytes. Dysfunctional development of NSPCs under the influence of IFN gamma was finally demonstrated by applying the microelectrode array technology. IFN gamma exposure of NSPCs during an initial 7-day proliferation period prevented the subsequent adequate differentiation and formation of functional neuronal networks. Conclusions: Our results show that immunocytochemical analyses of NSPC-derived progeny are not necessarily indicating the correct cellular phenotype specifically under inflammatory conditions and that simultaneous expression of neuronal and glial markers rather point to cellular dysregulation. We hypothesize that inhibiting the impact of IFN gamma on NSPCs during neurological diseases might contribute to effective neurogenesis and regeneration.