The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair

Nina S Corsini; Ignacio Sancho-Martinez; Sabrina Laudenklos; Désirée Glagow; Sachin Kumar; Elisabeth Letellier; Philipp Koch; Marcin Teodorczyk; Susanne Kleber; Stefan Klussmann; Benedict Wiestler; Oliver Brüstle; Wolf Mueller; Christian Gieffers; Oliver Hill; Meinolf Thiemann; Matthias Seedorf; Norbert Gretz; Rolf Sprengel; Tansu Celikel; Ana Martin-Villalba

doi:10.1016/j.stem.2009.05.004

The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair

Nina S Corsini, Ignacio Sancho-Martinez, Sabrina Laudenklos, Désirée Glagow, Sachin Kumar, Elisabeth Letellier, Philipp Koch, Marcin Teodorczyk, Susanne Kleber, Stefan Klussmann, Benedict Wiestler, Oliver Brüstle, Wolf Mueller, Christian Gieffers, Oliver Hill, Meinolf Thiemann, Matthias Seedorf, Norbert Gretz, Rolf Sprengel, Tansu CelikelAna Martin-Villalba

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

112 Citations (Scopus)

Abstract

Adult 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.

Original language	English
Pages (from-to)	178-190
Number of pages	13
Journal	Cell Stem Cell
Volume	5
Issue number	2
DOIs	https://doi.org/10.1016/j.stem.2009.05.004
Publication status	Published - 7 Aug 2009

Keywords

Adult Stem Cells
Animals
Antigens, CD95
Brain
Brain Ischemia
Fas Ligand Protein
Female
Gene Expression
Memory
Mice
Mice, Inbred C57BL
Neurogenesis
Neurons
Protein Kinases
Signal Transduction
Stem Cell Transplantation
TOR Serine-Threonine Kinases

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Corsini, N. S., Sancho-Martinez, I., Laudenklos, S., Glagow, D., Kumar, S., Letellier, E., Koch, P., Teodorczyk, M., Kleber, S., Klussmann, S., Wiestler, B., Brüstle, O., Mueller, W., Gieffers, C., Hill, O., Thiemann, M., Seedorf, M., Gretz, N., Sprengel, R., ... Martin-Villalba, A. (2009). The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair. Cell Stem Cell, 5(2), 178-190. https://doi.org/10.1016/j.stem.2009.05.004

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abstract = "Adult 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.",

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Corsini, NS, Sancho-Martinez, I, Laudenklos, S, Glagow, D, Kumar, S, Letellier, E, Koch, P, Teodorczyk, M, Kleber, S, Klussmann, S, Wiestler, B, Brüstle, O, Mueller, W, Gieffers, C, Hill, O, Thiemann, M, Seedorf, M, Gretz, N, Sprengel, R, Celikel, T & Martin-Villalba, A 2009, 'The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair', Cell Stem Cell, vol. 5, no. 2, pp. 178-190. https://doi.org/10.1016/j.stem.2009.05.004

TY - JOUR

T1 - The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair

AU - Corsini, Nina S

AU - Sancho-Martinez, Ignacio

AU - Laudenklos, Sabrina

AU - Glagow, Désirée

AU - Kumar, Sachin

AU - Letellier, Elisabeth

AU - Koch, Philipp

AU - Teodorczyk, Marcin

AU - Kleber, Susanne

AU - Klussmann, Stefan

AU - Wiestler, Benedict

AU - Brüstle, Oliver

AU - Mueller, Wolf

AU - Gieffers, Christian

AU - Hill, Oliver

AU - Thiemann, Meinolf

AU - Seedorf, Matthias

AU - Gretz, Norbert

AU - Sprengel, Rolf

AU - Celikel, Tansu

AU - Martin-Villalba, Ana

PY - 2009/8/7

Y1 - 2009/8/7

N2 - Adult 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.

AB - Adult 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.

KW - Adult Stem Cells

KW - Animals

KW - Antigens, CD95

KW - Brain

KW - Brain Ischemia

KW - Fas Ligand Protein

KW - Female

KW - Gene Expression

KW - Memory

KW - Mice

KW - Mice, Inbred C57BL

KW - Neurogenesis

KW - Neurons

KW - Protein Kinases

KW - Signal Transduction

KW - Stem Cell Transplantation

KW - TOR Serine-Threonine Kinases

U2 - 10.1016/j.stem.2009.05.004

DO - 10.1016/j.stem.2009.05.004

M3 - Article

C2 - 19664992

SN - 1934-5909

VL - 5

SP - 178

EP - 190

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 2

ER -

The Death Receptor CD95 Activates Adult Neural Stem Cells for Working Memory Formation and Brain Repair

Abstract

Keywords

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