Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 49, Pages 11205-11213Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1436-04.2004
Keywords
adult neurogenesis; Bax; cell death; mouse; proliferation; migration; differentiation
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Funding
- NINDS NIH HHS [R01 NS020402, NS20402] Funding Source: Medline
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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.
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