title: The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair.
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.
authors: Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany.
authors: Nina S
authors: NS
authors: Corsini
authors: Ignacio
authors: I
authors: Sancho-Martinez
authors: Sabrina
authors: S
authors: Laudenklos
authors: Désirée
authors: D
authors: Glagow
authors: Sachin
authors: S
authors: Kumar
authors: Elisabeth
authors: E
authors: Letellier
authors: Philipp
authors: P
authors: Koch
authors: Marcin
authors: M
authors: Teodorczyk
authors: Susanne
authors: S
authors: Kleber
authors: Stefan
authors: S
authors: Klussmann
authors: Benedict
authors: B
authors: Wiestler
authors: Oliver
authors: O
authors: Brüstle
authors: Wolf
authors: W
authors: Mueller
authors: Christian
authors: C
authors: Gieffers
authors: Oliver
authors: O
authors: Hill
authors: Meinolf
authors: M
authors: Thiemann
authors: Matthias
authors: M
authors: Seedorf
authors: Norbert
authors: N
authors: Gretz
authors: Rolf
authors: R
authors: Sprengel
authors: Tansu
authors: T
authors: Celikel
authors: Ana
authors: A
authors: Martin-Villalba
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000628:therapy; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D033581:Stem Cell Transplantation; D058570:TOR Serine-Threonine Kinases; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases