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 journalArticlepeer-review

    165 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

    • General Neuroscience

    Fingerprint

    Dive into the research topics of 'Programmed cell death of adult-generated hippocampal neurons is mediated by the proapoptotic gene bax'. Together they form a unique fingerprint.

    Cite this