Exercise enhances learning and hippocampal neurogenesis in aged mice

Abstract

Aging causes changes in the hippocampus that may lead to cognitive decline in older adults. In young animals, exercise increases hippocampal neurogenesis and improves learning. We investigated whether voluntary wheel running would benefit mice that were sedentary until 19 months of age. Specifically, young and aged mice were housed with or without a running wheel and injected with bromodeoxyuridine or retrovirus to label newborn cells. After 1 month, learning was tested in the Morris water maze. Aged runners showed faster acquisition and better retention of the maze than age-matched controls. The decline in neurogenesis in aged mice was reversed to 50% of young control levels by running. Moreover, fine morphology of new neurons did not differ between young and aged runners, indicating that the initial maturation of newborn neurons was not affected by aging. Thus, voluntary exercise ameliorates some of the deleterious morphological and behavioral consequences of aging.

Figure 1.

Water maze learning in young and aged mice housed with or without running wheel access. Aged controls (O) had significantly longer latency (a) and swim path (b) to the platform than all other groups (p < 0.01). Swim speed (c) was slower in old controls than in all other groups on day 5 of training (p < 0.03). The probe test 4 h after the last trial on day 5 showed that YR mice (d, f) and OR mice (h) had a significant preference for the platform quadrant but not the Y mice (e) and O mice (g). Asterisks indicate a significant difference from YR and OR mice (*) and a significant difference from all other groups/quadrants (**); the filled circle indicates a significant difference from adjacent quadrants (p < 0.05).

Figure 2.

Neurogenesis in the young and aged dentate gyrus. Confocal images of immunofluorescent triple-labeled sections for BrdU (red), NeuN (green), and S100β (blue) [BrdU-labeled neurons are orange(redplusgreen)]inyoungcontrols(a), old controls (c), young runners (b), and old runners (d) are shown, as well as photomicrographs of GFP⁺ new neurons in young (e) and aged (g) running mice at 4 weeks after virus injection. The boxed areas in e and f correspond to the enlarged images of spines in young (f) and aged (h) mice (DAPI, blue).

Figure 3.

Blood vessel size in the dentate gyrus of young and aged mice housed with or without a running wheel. a, The perimeter of the vessels is larger in YR mice compared with age-matchedcontrols(Y;p<0.04) but did not differ from the aged controls (O) or aged runners (OR) (p > 0.21). b, Vessel surface area was greater in YR mice than in all of the other groups (p < 0.05). c, Lectin-stained vessels (red) and DAPI (blue) in the dentate gyrus.