Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging

eLife

Sebastian Jessberger¹  John Darby Cole¹  Daniel Gonzalez-Bohorquez¹  Jacobo Sarabia del Castillo²  Gabriele Gut²  Lucas Pelkmans² 

[1] Brain Research Institute, University of Zurich, Zurich, Switzerland;Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland;

关键词: neurogenesis;    hippocampus;    stem cell;    aging;    Human;    Mouse;   

DOI  :  10.7554/eLife.68000

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Advancing age causes reduced hippocampal neurogenesis, associated with age-related cognitive decline. The spatial relationship of age-induced alterations in neural stem cells (NSCs) and surrounding cells within the hippocampal niche remains poorly understood due to limitations of antibody-based cellular phenotyping. We established iterative indirect immunofluorescence imaging (4i) in tissue sections, allowing for simultaneous detection of 18 proteins to characterize NSCs and surrounding cells in 2-, 6-, and 12-month-old mice. We show that reorganization of the dentate gyrus (DG) niche already occurs in middle-aged mice, paralleling the decline in neurogenesis. 4i-based tissue analysis of the DG identifies changes in cell-type contributions to the blood-brain barrier and microenvironments surrounding NSCs to play a pivotal role to preserve neurogenic permissiveness. The data provided represent a resource to characterize the principles causing alterations of stem cell-associated plasticity within the aging DG and provide a blueprint to analyze somatic stem cell niches across lifespan in complex tissues.

【 授权许可】

CC BY