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For example, the volume of the hippocampus in older adults is positively associated with physical activity ( 54) and aerobic fitness ( 10, 15). More specifically, the hippocampus is involved in learning, memory, and stress resilience, and it uniquely adapts to the level of physical activity. Physical exercise or a greater than average level of physical activity is known to improve a wide range of brain functions ( 14, 21, 30). This study indicates that cessation of exercise or a decrease in physical activity is associated with an increased risk for impaired hippocampal function, which might increase vulnerability to stress-induced mood disorders. Forced treadmill running following exercise cessation failed to prevent the negative neurogenesis rebound. Importantly, exercise cessation suppressed ambulatory activity, and a significant correlation between change in activity and DCX-positive neuron density suggested that the decrease in activity is involved in neurogenesis impairment. Neither elevated expression of ΔFosB, a transcription factor involved in neurogenesis regulation, nor increased plasma corticosterone, were involved in the negative neurogenesis rebound. Immunohistochemistry analysis suggests that the negative rebound in neurogenesis is caused by diminished cell survival, not by suppression of cell proliferation and neural maturation. Following exercise cessation, the density of DCX-positive neurons gradually decreased and was significantly lower than that in the Con group at 5 and 8 wk after cessation, indicating that exercise cessation leads to a negative rebound in hippocampal neurogenesis. Exercise resulted in a significant increase in the density of doublecortin (DCX)-positive immature neurons in the dentate gyrus (at week 0). Mice in the ExC group were reared in a cage with a running wheel for 8 wk and subsequently placed in a standard cage to cease the exercise. Male C57BL/6 mice were randomly assigned to either a control (Con) or an exercise cessation (ExC) group. This study examined the time-course profile of hippocampal neurogenesis following exercise cessation. Physical exercise can improve brain function, but the effects of exercise cessation are largely unknown.