The nuclear receptor REV-ERBα regulates Fabp7 and modulates adult hippocampal neurogenesis

PLoS One. 2014 Jun 16;9(6):e99883. doi: 10.1371/journal.pone.0099883. eCollection 2014.

Abstract

The function of the nuclear receptor Rev-erbα (Nr1d1) in the brain is, apart from its role in the circadian clock mechanism, unknown. Therefore, we compared gene expression profiles in the brain between wild-type and Rev-erbα knock-out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a direct target of repression by REV-ERBα. Loss of Rev-erbα manifested in memory and mood related behavioral phenotypes and led to overexpression of Fabp7 in various brain areas including the subgranular zone (SGZ) of the hippocampus, where neuronal progenitor cells (NPCs) can initiate adult neurogenesis. We found increased proliferation of hippocampal neurons and loss of its diurnal pattern in Rev-erbα KO mice. In vitro, proliferation and migration of glioblastoma cells were affected by manipulating either Fabp7 expression or REV-ERBα activity. These results suggest an important role of Rev-erbα and Fabp7 in adult neurogenesis, which may open new avenues for treatment of gliomas as well as neurological diseases such as depression and Alzheimer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affect / physiology
  • Aging / metabolism*
  • Animals
  • Behavior, Animal
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Circadian Rhythm
  • Cognition
  • Dentate Gyrus / metabolism
  • Fatty Acid-Binding Protein 7
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Humans
  • Immunohistochemistry
  • Mice, Knockout
  • Neurogenesis*
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / deficiency
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Carrier Proteins
  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • RNA, Messenger
  • Tumor Suppressor Proteins

Grant support

Funding by the Swiss National Science Foundation, the Velux Foundation and the State of Fribourg is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.