Programmed cell death of adult-generated hippocampal neurons is mediated by the proapoptotic gene bax

Woong Sun, Adam Winseck, Sharon Vinsant, Ok Hee Park, Hyun Kim, Ronald W. Oppenheim

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

In the dentate gyrus (DG) of the adult mouse hippocampus, a substantial number of new cells are generated daily, but only a subset of these survive and differentiate into mature neurons, whereas the majority undergo programmed cell death (PCD). However, neither the intracellular machinery required for adult stem cell-derived neuronal death nor the biological implications of the significant loss of these newly generated cells have been examined. Several markers for apoptosis failed to reveal cell death in Bax-deficient mice, and this, together with a progressive increase in neuron number in the DG of the Bax knock-out, indicates that Bax is critical for the PCD of adult-generated hippocampal neurons. Whereas the proliferation of neural progenitor cells was not altered in the Bax-knock-out, there was an accumulation of doublecortin, calretinin+, and neuronal-specific nuclear protein+ postmitotic neurons, suggesting that Bax-mediated PCD of adult-generated neurons takes place during an early phase of differentiation. The absence of PCD in the adult also influenced the migration and maturation of adult-generated DG neurons. These results suggest that PCD in the adult brain plays a significant role in the regulation of multiple aspects of adult neurogenesis.

Original languageEnglish
Pages (from-to)11205-11213
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number49
DOIs
Publication statusPublished - 2004 Dec 8

Keywords

  • Adult neurogenesis
  • Bax
  • Cell death
  • Differentiation
  • Migration
  • Mouse
  • Proliferation

ASJC Scopus subject areas

  • Neuroscience(all)

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