Effects of Voluntary Wheel-Running Types on Hippocampal Neurogenesis and Spatial Cognition in Middle-Aged Mice

While increasing evidence demonstrated that voluntary wheel running promotes cognitive function, little is known on how different types of voluntary wheel running affect cognitive function in elderly populations. We investigated the effects of various voluntary wheel-running types on adult hippocampal neurogenesis and spatial cognition in middle-aged mice. Male C57BL6 and Thy1-green fluorescent protein (GFP) transgenic mice (13 months) were equally assigned to one of the following groups: (1) T1: no voluntary wheel running; (2) T2: intermittent voluntary wheel running; and (3) T3: continuous voluntary wheel running. The Thy1-GFP transgenic mice were used to specifically label granule cells, since Thy-1 is a promoter for neuronal expression. Behavioral evaluations suggested that intermittent voluntary wheel running improved Morris water maze performance in middle-aged mice. The number of BrdU-positive cells was significantly higher in both intermittent and continuous voluntary wheel running compared with no voluntary wheel running. However, only intermittent voluntary wheel running facilitated the newborn cells to differentiate into granule cells, while newborn cells tended to differentiate into astrocytes and repopulation of microglia was also enhanced in the continuous voluntary wheel-running group. These results indicated that intermittent voluntary exercise may be more beneficial for enhancing spatial memory. Effective improvement of hippocampal neurogenesis was also caused by intermittent voluntary wheel running in middle-aged mice.