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Running increases the number of new granule neurons in the dentate gyrus but prevents stress-induced increases in IEG expression in new and mature granule cells. These mice ran or were sedentary for 6 weeks, received BrdU injections from days 2–15 of the experiment, and were perfused 30 min after cold water swim stress or no stress. A, Long-term running increases the number of BrdU-labeled cells in both dorsal and ventral dentate gyrus of adult mice. B, Photomicrographs of BrdU-labeled cells (arrowheads) in the dentate gyrus that are more numerous in runner than sedentary mice. C, Cold water swim stress increases the percentage of new neurons (BrdU-labeled cells) that express c-fos or arc in sedentary, but not runner, mice. D, Confocal images of cells (arrows) labeled with BrdU (red) and c-fos (green) or arc (green). E, Cold water swim stress increases the number of granule cells that express c-fos or arc in sedentary but not runner mice. F, Photomicrographs of c-fos (left) and arc (right) positive cells in the dentate gyrus. Error bars represent SEM. *p < 0.05 compared with Sed for A; compared with no stress Sed for C, E. Scale bars: in B, F, 20 μm; in D, 10 μm.

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