Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis.

Autor: Bedrosian TA; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Houtman J; Nuclear Architecture in Neural Plasticity and Aging, German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany., Eguiguren JS; Nuclear Architecture in Neural Plasticity and Aging, German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany., Ghassemzadeh S; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Rund N; Nuclear Architecture in Neural Plasticity and Aging, German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany., Novaresi NM; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Hu L; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Parylak SL; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Denli AM; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Randolph-Moore L; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Namba T; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.; Neuroscience Center, HiLIFE-Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Gage FH; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA., Toda T; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Nuclear Architecture in Neural Plasticity and Aging, German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Paul F. Glenn Center for Biology of Aging Research at the Salk Institute, La Jolla, CA, USA.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2021 Feb 01; Vol. 40 (3), pp. e105819. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.15252/embj.2020105819
Abstrakt: Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age-dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age-related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age-related anxiety-like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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