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

Abstract

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 young and aged mice. We show that reorganization of the DG niche already occurs in middle-aged mice, paralleling the decline in neurogenesis. Tissue 4i-based 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.