Ligand-binding/transcriptional repressor domain-deficient REV-ERBβ inhibits dendrite and spine formation of newborn adult hippocampal neurons

Abstract

REV-ERB{beta} is a transcriptional repressor of nuclear receptors that regulates the circadian rhythm and plays an important role in regulation of the proliferation, differentiation, and maturation of neurons. Dysregulation of the circadian rhythm has been associated with neuropsychiatric disorders, and activation of REV-ERBs can induce anxiolytic behavior in mice. Furthermore, hippocampal neurogenesis is important in the effects of antidepressants. However, the role of REV-ERB{beta} in adult hippocampal neurogenesis in vivo at the single-cell level is not known. In this study, protein localization of REV-ERB{beta} in the subgranular zone of the hippocampal dentate gyrus (DG) was mainly shown in NeuN-positive neurons, and the effect of expressing a dominant negative form of REV-ERB{beta} lacking the C-terminal region on newborn neurons in the hippocampal DG of adult mice was examined to investigate the role of REV-ERB{beta} in neurogenesis. A retroviral vector containing the dominant negative REV-ERB{beta} or a control vector was injected into the mouse DG. At 4 weeks after injection, the morphology of dendrites and dendritic spines of newborn neurons labeled by the virus was examined. Expression of the dominant negative form of REV-ERB{beta} inhibited dendrite outgrowth and branching and decreased dendritic spine formation in newborn neurons in the adult mouse hippocampal DG. This study revealed a new role for REV-ERB&{beta} in adult hippocampal neurogenesis at the single cell level, and the results will provide insight into neurogenesis in the adult brain and its relationship with psychiatric disorders.