title: Survival of adult generated hippocampal neurons is altered in circadian arrhythmic mice.
abstract: The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well. In the present study, neurogenesis in the hippocampal subgranular zone was examined in arrhythmic Bmal1 knockout (-KO) mice and their rhythmic heterozygous and wildtype littermates. Proliferation and survival of newly generated subgranular zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a measure of cell death) and hippocampal volume were examined in cresyl violet stained sections. There was no significant difference in cellular proliferation between any of the groups, yet survival of proliferating cells, 6 weeks after the bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals. The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet hippocampal volume remained the same across genotypes. These findings suggest that while a functional circadian clock is not necessary for normal proliferation of neuronal precursor cells, the normal pruning of newly generated neurons in the hippocampus may require a functional circadian clock.
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Brooke D
authors.initials: BD
authors.lastname: Rakai
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Department of Neuroscience, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chrusch
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Spanswick
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Dyck
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pharmacology & Therapeutics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000375:Aging / Q000473:pathology*; D000818:Animals; D001522:Behavior, Animal; D049109:Cell Proliferation; D002470:Cell Survival; D002940:Circadian Rhythm; D018891:Dentate Gyrus / Q000473:pathology; D006579:Heterozygote; D006624:Hippocampus / Q000473:pathology*; D006720:Homozygote; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology*; D009929:Organ Size
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse