title: Age-related decline in BubR1 impairs adult hippocampal neurogenesis.
abstract: Aging causes significant declines in adult hippocampal neurogenesis and leads to cognitive disability. Emerging evidence demonstrates that decline in the mitotic checkpoint kinase BubR1 level occurs with natural aging and induces progeroid features in both mice and children with mosaic variegated aneuploidy syndrome. Whether BubR1 contributes to age-related deficits in hippocampal neurogenesis is yet to be determined. Here we report that BubR1 expression is significantly reduced with natural aging in the mouse brain. Using established progeroid mice expressing low amounts of BubR1, we demonstrate these mice exhibit deficits in neural progenitor proliferation and maturation, leading to reduction in new neuron production. Collectively, our identification of BubR1 as a new and critical factor controlling sequential steps across neurogenesis raises the possibility that BubR1 may be a key mediator regulating aging-related hippocampal pathology. Targeting BubR1 may represent a novel therapeutic strategy for age-related cognitive deficits.
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.|Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.
authors.forename: Zhongxi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Heechul
authors.initials: H
authors.lastname: Jun
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Chan-Ii
authors.initials: CI
authors.lastname: Choi
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Syed Mohammed Qasim
authors.initials: SMQ
authors.lastname: Hussaini
authors.affiliation: Department of Anatomy and Cell Biology, Shriners Hospital for Children Pediatric Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
authors.forename: Ambrosia J
authors.initials: AJ
authors.lastname: Simmons
authors.affiliation: Department of Anatomy and Cell Biology, Shriners Hospital for Children Pediatric Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
authors.forename: Seonhee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.|Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.|Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Baker
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.|Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Mi-Hyeon
authors.initials: MH
authors.lastname: Jang
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D064111:Minichromosome Maintenance Complex Component 2 / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D011371:Progeria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; D000089622:Doublecortin Domain Proteins; C576318:Mcm2 protein, mouse; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; D064111:Minichromosome Maintenance Complex Component 2
keywords: Adult neurogenesis; aging; bubR1; dendrite morphogenesis; hippocampus; progeroid mouse model