title: The nuclear receptor REV-ERBα regulates Fabp7 and modulates adult hippocampal neurogenesis.
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.
authors.affiliation: Dept. of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Schnell
authors.affiliation: Dept. of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chappuis
authors.affiliation: Dept. of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schmutz
authors.affiliation: Dept. of Medicine, Unit of Anatomy, University of Fribourg, Fribourg, Switzerland.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Brai
authors.affiliation: Dept. of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Ripperger
authors.affiliation: NCCR frontiers in Genetics, University of Geneva, Geneva, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schaad
authors.affiliation: Dept. of Anatomy, University of Zürich, Zürich, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Welzl
authors.affiliation: NCCR frontiers in Genetics, University of Geneva, Geneva, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.affiliation: Dept. of Medicine, Unit of Anatomy, University of Fribourg, Fribourg, Switzerland.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Alberi
authors.affiliation: Dept. of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Albrecht
mesh_terms: D000339:Affect / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002940:Circadian Rhythm; D003071:Cognition; D018891:Dentate Gyrus / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018345:Mice, Knockout; D055495:Neurogenesis; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000172:deficiency / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins