title: Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory.
abstract: Presenilin-1 (PS1), the catalytic core of the aspartyl protease γ-secretase, regulates adult neurogenesis. However, it is not clear whether the role of neurogenesis in hippocampal learning and memory is PS1-dependent, or whether PS1 loss of function in adult hippocampal neurogenesis can cause learning and memory deficits. Here we show that downregulation of PS1 in hippocampal neural progenitor cells causes progressive deficits in pattern separation and novelty exploration. New granule neurons expressing reduced PS1 levels exhibit decreased dendritic branching and dendritic spines. Further, they exhibit reduced survival. Lastly, we show that PS1 effect on neurogenesis is mediated via β-catenin phosphorylation and notch signaling. Together, these observations suggest that impairments in adult neurogenesis induce learning and memory deficits and may play a role in the cognitive deficits observed in Alzheimer's disease.
authors.affiliation: Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America; Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Bonds
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America.
authors.forename: Yafit
authors.initials: Y
authors.lastname: Kuttner-Hirshler
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Bartolotti
authors.affiliation: Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America; Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America; Medical Scientist Training Program, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Tobin
authors.affiliation: Midwestern University, 555 31st street, Downers Grove, IL, 60515, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Pizzi
authors.affiliation: Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, 60064, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Marr
authors.affiliation: Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America; Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612, United States of America.
authors.forename: Orly
authors.initials: O
authors.lastname: Lazarov
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D010766:Phosphorylation; D053764:Presenilin-1 / Q000502:physiology*; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051176:beta Catenin / Q000502:physiology
chemical_list: D053764:Presenilin-1; D051880:Receptors, Notch; D051176:beta Catenin