Cargando…
BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus
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 mediat...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039291/ https://www.ncbi.nlm.nih.gov/pubmed/21364616 http://dx.doi.org/10.1038/cddis.2009.13 |
_version_ | 1782198178348531712 |
---|---|
author | Bunk, E C König, H-G Bernas, T Engel, T Henshall, D C Kirby, B P Prehn, J H M |
author_facet | Bunk, E C König, H-G Bernas, T Engel, T Henshall, D C Kirby, B P Prehn, J H M |
author_sort | Bunk, E C |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3039291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-30392912011-02-24 BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus Bunk, E C König, H-G Bernas, T Engel, T Henshall, D C Kirby, B P Prehn, J H M Cell Death Dis Original Article 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. Nature Publishing Group 2010-01 2010-01-21 /pmc/articles/PMC3039291/ /pubmed/21364616 http://dx.doi.org/10.1038/cddis.2009.13 Text en Copyright © 2010 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This article is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Bunk, E C König, H-G Bernas, T Engel, T Henshall, D C Kirby, B P Prehn, J H M BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
title | BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
title_full | BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
title_fullStr | BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
title_full_unstemmed | BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
title_short | BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
title_sort | bh3-only proteins bim and puma in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039291/ https://www.ncbi.nlm.nih.gov/pubmed/21364616 http://dx.doi.org/10.1038/cddis.2009.13 |
work_keys_str_mv | AT bunkec bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus AT konighg bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus AT bernast bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus AT engelt bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus AT henshalldc bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus AT kirbybp bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus AT prehnjhm bh3onlyproteinsbimandpumaintheregulationofsurvivalandneuronaldifferentiationofnewlygeneratedcellsintheadultmousehippocampus |