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We have previously suggested that progranulin mediates the stimulatory effects of estrogen on adult neurogenesis in the hippocampus. Neurogenesis in mature animals is enhanced by growth factors, environmental enrichment, and voluntary exercise. In this study, we investigated the role of progranulin in voluntary running-induced hippocampal neurogenesis. In the hippocampus of wild-type mice, the pyramidal neurons in the CA1 and CA3 regions and interneurons in the hilus were mainly immunoreactive for progranulin, and wheel running increased progranulin expression in these neurons. Wheel running also increased the number of proliferating cells in the hippocampus in wild-type mice, but not in progranulin-deficient mice. These results suggest that progranulin plays an indispensable role in enhancing the hippocampal neurogenesis induced by voluntary exercise.