Peer Reviewed

1

Document Type

Article

Publication Date

2010

Keywords

Animals, Apoptosis, Apoptosis Regulatory Proteins, Bromodeoxyuridine, Cell Differentiation, Cell Survival, Cells, Cultured, Hippocampus, Membrane Proteins, Mice, Microtubule-Associated Proteins, Neurogenesis, Neurons, Neuropeptides, Phenotype, Proto-Oncogene Proteins, Tumor Suppressor Proteins

Funder/Sponsor

Science Foundation Ireland, National Biophotonics and Imaging Platform Ireland (Higher Education Authority).

Comments

The original article is available at www.nature.com

Abstract

Neurogenesis persists in the adult hippocampus, where several thousand neurons are born every day. Most of the newly generated cells are eliminated by apoptosis, possibly because of their failure to integrate properly into neural networks. The BH3-only proteins Bim and Puma have been shown to mediate trophic factor withdrawal- and anoikis-induced apoptosis in various systems. We therefore determined their impact on proliferation, survival, and differentiation of adult-generated cells in the mouse hippocampus using gene-deficient mice. Wild-type, bim-, and puma-deficient mice showed similar rates of precursor cell proliferation, as evidenced by 5-bromo-2-deoxyuridine (BrdU)-incorporation. Deficiency in either bim or puma significantly increased the survival of adult-born cells in the dentate gyrus (DG) after 7 days. Consistently, we detected increased numbers of doublecortin (DCX)-positive and fewer terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelled-positive cells in the DG of bim- and puma-deficient mice. Bim and puma deficiency did not change early markers of neuronal differentiation, as evidenced by BrdU/DCX double-labelling. However, BrdU/NeuN double-labelling revealed that deficiency of bim, but not puma, accelerated the differentiation of newly generated cells into a neuronal phenotype. Our data show that Bim and Puma are prominently involved in the regulation of neuronal progenitor cell survival in the adult DG, but also suggest that Bim has an additional role in neuronal differentiation of adult-born neural precursor cells.

Disciplines

Physics | Physiology

Citation

Bunk EC, König HG, Bernas T, Engel T, Henshall DC, Kirby BP, Prehn JH. BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus. Cell Death & Disease. 2010;1:e15.

PubMed ID

21364616

DOI Link

10.1038/cddis.2009.13

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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