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

被引：115

作者：

Corsini, Nina S. ^{[1
]}

Sancho-Martinez, Ignacio ^{[1
]}

Laudenklos, Sabrina ^{[1
]}

Glagow, Desiree ^{[1
]}

Kumar, Sachin ^{[1
]}

Letellier, Elisabeth ^{[1
]}

Koch, Philipp ^{[6
,7
]}

Teodorczyk, Marcin ^{[1
]}

Kleber, Susanne ^{[1
]}

Klussmann, Stefan ^{[1
]}

Wiestler, Benedict ^{[1
]}

Bruestle, Oliver ^{[6
,7
]}

Mueller, Wolf ^{[9
]}

Gieffers, Christian ^{[5
]}

Hill, Oliver ^{[5
]}

Thiemann, Meinolf ^{[5
]}

Seedorf, Matthias ^{[2
]}

Gretz, Norbert ^{[8
]}

Sprengel, Rolf ^{[3
]}

Celikel, Tansu ^{[4
]}

Martin-Villalba, Ana ^{[1
]}

机构：

[1] German Canc Res Ctr, D-69120 Heidelberg, Germany

[2] Univ Heidelberg, Zentrum Mol Biol, D-69120 Heidelberg, Germany

[3] Max Planck Inst Med Res, Dept Mol Neurobiol, D-69120 Heidelberg, Germany

[4] Univ So Calif, Lab Neural Circuits & Plast, Los Angeles, CA 90089 USA

[5] Apogenix GmbH, D-69120 Heidelberg, Germany

[6] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany

[7] Hertie Fdn, D-53127 Bonn, Germany

[8] Univ Heidelberg, Med Res Ctr, Med Fac Mannheim, D-68135 Mannheim, Germany

[9] Univ Heidelberg, Inst Pathol, Dept Neuropathol, D-69120 Heidelberg, Germany

来源：

CELL STEM CELL | 2009年 / 5卷 / 02期

关键词：

FAS-INDUCED APOPTOSIS; HIPPOCAMPAL NEUROGENESIS; SUBVENTRICULAR ZONE; MICE; NEURONS; PROGENITORS; DIFFERENTIATION; REGENERATION; TRANSLATION; REPLACEMENT;

D O I：

10.1016/j.stem.2009.05.004

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页码：178 / 190

页数：13

共 45 条

[1]

ABERRANT TRANSCRIPTION CAUSED BY THE INSERTION OF AN EARLY TRANSPOSABLE ELEMENT IN AN INTRON OF THE FAS ANTIGEN GENE OF LPR MICE [J].