1. Programmed Cell Death of Adult-Generated Hippocampal Neurons Is Mediated by the Proapoptotic Gene Bax
- Author
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Woong Sun, Ronald W. Oppenheim, Hyun Kim, Ok Hee Park, Adam K. Winseck, and Sharon Vinsant
- Subjects
Aging ,Programmed cell death ,Development/Plasticity/Repair ,Apoptosis ,Hippocampal formation ,Hippocampus ,Mice ,Cell Movement ,In Situ Nick-End Labeling ,medicine ,Animals ,Cell Proliferation ,bcl-2-Associated X Protein ,Mice, Knockout ,Neurons ,biology ,General Neuroscience ,Dentate gyrus ,Neurogenesis ,Cell Differentiation ,Neural stem cell ,Doublecortin ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Bromodeoxyuridine ,Proto-Oncogene Proteins c-bcl-2 ,nervous system ,Dentate Gyrus ,biology.protein ,Neuron ,Neuroscience - 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.
- Published
- 2004
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