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

Anna Schnell; Sylvie Chappuis; Isabelle Schmutz; Emanuele Brai; Jürgen A Ripperger; Olivier Schaad; Hans Welzl; Patrick Descombes; Lavinia Alberi; Urs Albrecht

doi:10.1371/journal.pone.0099883

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.

Authors

Affiliations

¹ Dept. of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
² Dept. of Medicine, Unit of Anatomy, University of Fribourg, Fribourg, Switzerland.
³ NCCR frontiers in Genetics, University of Geneva, Geneva, Switzerland.
⁴ Dept. of Anatomy, University of Zürich, Zürich, Switzerland.

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

Grants and funding

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.