Bcl2 ‐expressing quiescent type B neural stem cells in the V‐SVZ are resistant to concurrent temozolomide/X‐irradiation

The brain's V ‐SVZ is a site of type B NSC‐mediated neurogenesis and unfortunately for very aggressive GBM. Treatment for GBM consists of resection, concurrent temozolomide (TMZ) and X‐irradiation (XRT) followed by adjuvant TMZ. We show that concurrent TMZ/XRT followed by adjuvant TMZ induces apoptosis in t ype A neuroblasts. In contrast, quiescent NSCs, which express high levels Bcl2 and Mcl1, survive and repopulate type A neuroblasts. AbstractThe ventricular ‐subventricular zone (V‐SVZ) of the mammalian brain is a site of adult neurogenesis. Within the V‐SVZ reside type B neural stem cells (NSCs) and type A neuroblasts. The V‐SVZ is also a primary site for very aggressive glioblastoma (GBM). Standard of care therapy for GBM consists of safe maxi mum resection, concurrent temozolomide (TMZ) and X‐irradiation (XRT) followed by adjuvant TMZ therapy. The question of how this therapy impacts neurogenesis is not well understood and is of fundamental importance as normal tissue tolerance is a limiting factor. Here, we studied the effects of conc urrent TMZ/XRT followed by adjuvant TMZ on type B stem cells and type A neuroblasts of the V‐SVZ in C57BL/6 mice. We found that chemo‐radiation induced an apoptotic response in type A neuroblasts, as marked by cleavage of Caspase‐3, but not in NSCs, and that A cells within the V‐SVZ were rep opulated given sufficient recovery time. 53BP1 foci formation and resolution was used to assess repair of DNA double strand br...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Translational and Clinical Research Source Type: research