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

EMBO J. 2021 Feb 1;40(3):e105819. doi: 10.15252/embj.2020105819. Epub 2020 Dec 10.

Abstract

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.

Keywords: adult hippocampal neurogenesis; lamin B1; mood regulation; stem cell aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Anxiety / genetics*
  • Cell Differentiation
  • Cell Line
  • Disease Models, Animal
  • Down-Regulation*
  • Female
  • Hippocampus / cytology*
  • Hippocampus / metabolism
  • Lamin Type B / genetics*
  • Lamin Type B / metabolism*
  • Male
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • Rats

Substances

  • Lamin Type B
  • lamin B1