死亡受体CD95激活成年神经干细胞以形成工作记忆并修复大脑。

The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair.

作者信息

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

机构信息

Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany.

出版信息

Cell Stem Cell. 2009 Aug 7;5(2):178-90. doi: 10.1016/j.stem.2009.05.004.

DOI:10.1016/j.stem.2009.05.004

PMID:19664992

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.

摘要

成体神经发生在脑室下区和齿状回持续存在，并且在中枢神经系统损伤时可被诱导。然而，新生神经元对神经网络的最终贡献是有限的。在此我们表明，在神经干细胞中，“死亡受体”CD95的刺激不会引发细胞凋亡，而是意外地导致干细胞存活率增加和神经元分化。这些效应是通过Src/PI3K/AKT/mTOR信号通路的激活介导的，最终导致蛋白质翻译的整体增加。CD95诱导神经发生在缺血性CA1区、未成熟的齿状回以及成年脑室下区强制表达CD95L后得到进一步证实。海马CD95的缺失导致神经发生减少和工作记忆缺陷。全脑缺血后，CD95介导的脑修复挽救了行为障碍。因此，我们将CD95/CD95L系统确定为持续的和损伤诱导的神经发生的指导性信号。