Aging brain microenvironment decreases hippocampal neurogenesis through Wnt‐mediated survivin signaling

Aging Cell

Carlos J. Miranda³  Lyndsey Braun³  Yuying Jiang³  Mark E. Hester³  Ling Zhang²  Matthew Riolo¹  Haijuan Wang¹  Meghan Rao³  Rachel A. Altura¹ 

[1] Division of Hematology-Oncology, Department of Pediatrics, Brown University, Providence, RI 02903, USA;Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;Center for Gene Therapy, Nationwide Children’s Hospital Research Institute, Columbus, OH 43205, USA

关键词: adult neurogenesis;    aging;    astrocytes;    survivin;    Wnt signaling;   

DOI  :  10.1111/j.1474-9726.2012.00816.x

来源: Wiley

【 摘 要 】

Summary

Accumulating evidence suggests that adult hippocampal neurogenesis relies on the controlled and continued proliferation of neural progenitor cells (NPCs). With age, neurogenesis decreases through mechanisms that remain unclear but are believed to involve changes in the NPC microenvironment. Here, we provide evidence that NPC proliferation in the adult brain is in part regulated by astrocytes via Wnt signaling and that this cellular cross-talk is modified in the aging brain, leading to decreased proliferation of NPCs. Furthermore, we show that astrocytes regulate the NPC cell cycle by acting on the expression levels of survivin, a known mitotic regulator. Among cell cycle genes found down-regulated in aged NPCs, survivin was the only one that restored NPC proliferation in the aged brain. Our results provide a mechanism for the gradual loss of neurogenesis in the brain associated with aging and suggest that targeted modulation of survivin expression directly or through Wnt signaling could be used to stimulate adult neurogenesis.

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland