Age-dependent remarkable regenerative potential of the dentate gyrus provided by intrinsic stem cells

Tamar Licht*, Tirzah Kreisel, Yoav Biala, Sandesh Mohan, Yoel Yaari, Andrey Anisimov, Kari Alitalo, Eli Keshet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Multiple insults to the brain lead to neuronal cell death, thus raising the question to what extent can lost neurons be replenished by adult neurogenesis. Here we focused on the hippocampus and especially the dentate gyrus (DG), a vulnerable brain region and one of the two sites where adult neuronal stem cells (NSCs) reside. While adult hippocampal neurogenesis was extensively studied with regard to its contribution to cognitive enhancement, we focused on their underestimated capability to repair a massively injured, nonfunctional DG. To address this issue, we inflicted substantial DG-specific damage in mice of either sex either by diphtheria toxin-based ablation of >50% of mature DG granule cells (GCs) or by prolonged brain-specific VEGF overexpression culminating in extensive, highly selective loss of DG GCs (thereby also reinforcing the notion of selective DG vulnerability). The neurogenic system promoted effective regeneration by increasing NSCs proliferation/survival rates, restoring a nearly original DG mass, promoting proper rewiring of regenerated neurons to their afferent and efferent partners, and regaining of lost spatial memory. Notably, concomitantly with the natural age-related decline in the levels of neurogenesis, the regenerative capacity of the hippocampus also subsided with age. The study thus revealed an unappreciated regenerative potential of the young DG and suggests hippocampal NSCs as a critical reservoir enabling recovery from catastrophic DG damage.

Original languageEnglish (US)
Pages (from-to)974-995
Number of pages22
JournalJournal of Neuroscience
Volume40
Issue number5
DOIs
StatePublished - Jan 29 2020

Keywords

  • Adult neurogenesis
  • Dentate gyrus
  • Hippocampal plasticity
  • Neural stem cells
  • Regeneration
  • VEGF

ASJC Scopus subject areas

  • Neuroscience(all)

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