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or an hour a da y, five days a week, mice in Hiro-

shi Maejima’s physiology lab at Hokkaido Uni-

versity in Sapporo, Japan, hit the treadmill. The

researcher’s goal in having the animals follow

the exercise routine isn’t to measure their mus-

cle mass or endurance. He wants to know how

exercise affects their brains.

Researchers have long recognized that exercise sharpens cer-

tain cognitive skills. Indeed, Maejima and his colleagues have

found that regular physical activity improves mice’s ability to

distinguish new objects from ones they’ve seen before. Over the

past 20 years, researchers have begun to get at the root of these

benefits, with studies pointing to increases in the volume of the

hippocampus, development of new neurons, and infiltration of

blood vessels into the brain. Now, Maejima and others are start-

ing to home in on the epigenetic mechanisms that drive the neu-

rological changes brought on by physical activity.

In October, Maejima’s team reported that the brains of

rodents that ran had greater than normal histone acetylation

in the hippocampus, the brain region considered the seat of

learning and memory.^1 The epigenetic marks resulted in higher

expression of Bdnf, the gene for brain-derived neurotrophic

factor (BDNF). By supporting the growth and maturation of

new nerve cells, BDNF is thought to promote brain health,

and higher levels of it correlate with improved cognitive per-

formance in mice and humans.

With a wealth of data on the benefits of working out emerging

from animal and human studies, clinicians have begun prescrib-

ing exercise to patients with neurodegenerative diseases such as

Parkinson’s and Alzheimer’s, as well as to people with other brain

disorders, from epilepsy to anxiety. Many clinical trials of exer-

cise interventions for neurodegenerative diseases, depression,

and even aging are underway. Promising results could bolster

the use of exercise as a neurotherapy.

“No one believes exercise is going to be a magic bullet,” says

Kirk Erickson, a cognitive psychologist at the University of

Pittsburgh. “But that doesn’t mean we shouldn’t do it.”

The body-brain connection

In the late 1990s, then-postdoc Henriette van Praag and other

members of Rusty Gage’s lab at the Salk Institute for Biological

Studies in La Jolla, California, were fascinated with recent find-

ings from the group showing that mice whose cages had toys and

running wheels developed more new neurons in the hippocam-

pus, a brain area important for learning and memory, than mice

living in less-stimulating enclosures. (See “Lab Toys,” The Scien-

tist, October 2009.)

Va n Praag wanted to identify which element of enriched environ-

ments had the greatest influence on the brain. She had some mice

learn to swim in a water maze, while others swam in open water, ran

on a running wheel, or interacted with several other mice. After 12

days, the development of new neurons was greatest in the group of