In the late 90's, work from the laboratory of Fred Gage, Salk Institute, La Jolla, California, showed that young mice produced more new neurons in the brain and gained significant cognitive benefit from voluntary exercise (see van Praag et al., 1999). Since then, students of Alzheimer disease and other forms of cognitive decline have wondered if the same might hold true in adult animals. The answer seems to come in positive.

Gage’s team has essentially repeated their earlier experiments using old mice, aged 19 months. First author Henriette van Praag and colleagues compared animals given free treadmill access to their couch potato littermates (no treadmills allowed). After 45 days, the aged but fitter mice that had been running an average of 3.9 Km per day did much better at remembering where a hidden platform was in the classic Morris water maze test. After five days of trials, for example, they only had to swim about 150 cm to find the platform, whereas the sedentary animals searched around for 500 cm before finding refuge.

The authors propose that cognitive improvement may be related to the production of new cells, particularly neurons, in the dentate gyrus of the hippocampus, an area of the brain that plays a key role in memory. They have no formal proof of this link, but offer an association. When van Praag and colleagues examined tissue sections, they found an average of 656 newborn cells in the hippocampus of exercising animals, and merely 117 neonatal cells in control mice. What’s more, in exercising mice, more than 25 percent of those newborn cells were neurons, compared to barely 10 percent in the control animals.

The study adds to a burgeoning literature that connects exercise with beneficial outcomes in the central nervous system. In rodents, exercise is known to increase synaptic plasticity (Farmer et al., 2004), expression of neurotrophic factors (see ARF related news story), spatial learning (see, for example, Fordyce and Farrar, 1991), and angiogenesis (Swain et al., 2003). In fact, in mouse models of AD, long-term exercise has also been shown to reduce the number of amyloid plaques that form in the brain (Adlard et al., 2005). Any number of these effects might explain why exercise can help people with AD (Teri et al., 2003). However, it should be noted that in this study, the researchers found that exercise had no effect on angiogenesis in the aged mice.—Tom Fagan.

Reference:
Van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J. Neurosci. September 21 2005;25:8580-8585. Abstract