Astrocytic Cx43 and Cx30 differentially modulate adult neurogenesis in mice

Abstract

In addition to their well known function in astrocyte coupling, gap junction forming connexins are also important for cell proliferation, migration and differentiation during brain development. The aim of this study was to determine whether loss of the main astrocytic connexins, connexin 43 (Cx43) or connexin 30 (Cx30), influences various stages of adult hippocampal neurogenesis. To that end, mice with a conditional Cx43 deletion in astrocytes and mice with a conventional knockout of Cx30 were used. We assessed cell proliferation based on Ki67-immunoreactive cell number and cell survival based on BrdU-immunoreactive cell number in the subgranular zone (SGZ) and the granular cell layer (GCL) of the dentate gyrus. The neuronal phenotype of surviving cells was analyzed following immunofluorescent co-localization of BrdU-positive cells with the neuronal markers doublecortin (DCX) and neuronal nuclear antigen (NeuN). Ablation of Cx43 in astrocytes significantly diminished proliferation and reduced the overall survival of newborn cells. In contrast, knockout of Cx30 showed a tendency towards increased proliferation and significantly enhanced the overall survival of newborn cells. The differentiation of surviving cells into neurons is unaffected following Cx43 or Cx30 knockout. Our data reveal that Cx43 promotes the survival of newborn neurons in the adult mouse hippocampus whereas Cx30 restricts their survival.