A simulation model of neuroprogenitor proliferation dynamics predicts age-related loss of hippocampal neurogenesis but not astrogenesis

Abstract

Adult hippocampal neuroprogenitors give rise to both neurons and astrocytes. As neuroprogenitors are lost with increased age, neurogenesis concomitantly decreases. However, the dynamics of neuron and astrocyte generation throughout adulthood has not been systematically examined. Here, we analyzed the hippocampal niche both longitudinally (from 2 h to 30d of cell life) and transversally (from 1 m to 12 m of age) and generated a Marsaglia polar random simulation model to predict newborn cell dynamics. The sharp decrease in newborn neuron production throughout adulthood was largely predicted by the number of proliferating neuroprogenitors at each age. In contrast, newborn astrocyte decay was slower and associated with their increased yield in mature mice. As a result, the niche shifted from neurogenic to neuro/astrogenic with increased age. Our data provide a simple "end-point" model to understand the hippocampal niche changes across adulthood and suggest yet unexplored functions of newborn astrocytes for the aging hippocampal circuitry.