Voluntary Exercise Alters the Cvto-architecture of the Adult Dentate Gyrus by Increasing Cellular Proliferation, Dendritic Complexity, and Spine Density

While a dramatic increase in the number of bromodeoxyuridine (BrdU)-positive cells in the adult dentate gyrus following voluntary exercise has been consistently reported, it has never been determined whether this reflects an increase in neurogenic activity or an exercise-induced increase in the metabolic processing of systemically injected BrdU (a compound that inserts itself into the D N A of cells undergoing replication in preparation for cell division). In these experiments, it is shown that (1) 200 mg/kg is a saturating dose of BrdU in both control and voluntary exercise animals, (2) there are almost twice as many BrdU-positive cells following exercise, but only i f doses of BrdU of 200 mg/kg or greater are employed, (3) high doses of BrdU (400 and 600 mg/kg) do not affect the appearance or distribution of labeled cells, (4) voluntary exercise leads to similar increases in the number of cells expressing Ki67, an intrinsic marker of cellular proliferation, (5) dendritic length and dendritic complexity are significantly increased in the dentate gyrus regions of animals that exercise, and (6) spine density is significantly greater on the dendrites of dentate granule cells following voluntary exercise. This study demonstrates that exercise up-regulates neurogenic activity in the dentate gyrus region of adult rats, independent of any putative changes in altered BrdU metabolism, and that it substantially alters the morphology of dentate granule cell dendrites. The dramatic changes to the cyto-architecture of the dentate gyrus induced by voluntary exercise may underlie the enhancement of hippocampal long-term potentiation and hippocampal-dependent memory that our group has previously described. These results suggest that exercise may be an effective component of therapeutic regimes aimed at improving the functioning of individuals with neuropathologies that involve the degradation of cells in the hippocampal dentate gyrus.