The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair
| Autor: | Marcin Teodorczyk, Norbert Gretz, B Wiestler, Meinolf Thiemann, Stefan Klussmann, Susanne Kleber, Tansu Celikel, Philipp Koch, Wolf Mueller, Rolf Sprengel, Sabrina Laudenklos, Oliver Brüstle, Ana Martin-Villalba, Elisabeth Letellier, Sachin Kumar, Ignacio Sancho-Martinez, Oliver Hill, Désirée Glagow, Nina S. Corsini, Christian Gieffers, Matthias Seedorf |
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| Rok vydání: | 2009 |
| Předmět: |
Epigenetic regulation of neurogenesis
Fas Ligand Protein Neurogenesis Subventricular zone Gene Expression Biology Biochemistry biophysics & molecular biology [F05] [Life sciences] Brain Ischemia Mice Memory medicine Genetics Animals fas Receptor Biochimie biophysique & biologie moléculaire [F05] [Sciences du vivant] PI3K/AKT/mTOR pathway Neurons Dentate gyrus TOR Serine-Threonine Kinases Brain brain damage Cell Biology STEMCELL Neural stem cell Neuroepithelial cell Mice Inbred C57BL neurogenesis Adult Stem Cells medicine.anatomical_structure nervous system Immunology CD95 Molecular Medicine Female Neuroscience Protein Kinases Adult stem cell Signal Transduction Stem Cell Transplantation |
| Zdroj: | Cell Stem Cell Cell Stem Cell, 5. (2009). |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2009.05.004 |
| Popis: | SummaryAdult neurogenesis persists in the subventricular zone and the dentate gyrus and can be induced upon central nervous system injury. However, the final contribution of newborn neurons to neuronal networks is limited. Here we show that in neural stem cells, stimulation of the “death receptor” CD95 does not trigger apoptosis but unexpectedly leads to increased stem cell survival and neuronal specification. These effects are mediated via activation of the Src/PI3K/AKT/mTOR signaling pathway, ultimately leading to a global increase in protein translation. Induction of neurogenesis by CD95 was further confirmed in the ischemic CA1 region, in the naive dentate gyrus, and after forced expression of CD95L in the adult subventricular zone. Lack of hippocampal CD95 resulted in a reduction in neurogenesis and working memory deficits. Following global ischemia, CD95-mediated brain repair rescued behavioral impairment. Thus, we identify the CD95/CD95L system as an instructive signal for ongoing and injury-induced neurogenesis. |
| Databáze: | OpenAIRE |
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