Brain saver. Mice in cages with toys and exercise equipment develop less brain amyloid than do ones in normal cages (inset).

Brain Suffers from Boring Life

A life full of exercise and play can protect mice from the buildup of protein clumps in the brain that scientists believe play a key role in Alzheimer's disease, according to a new study. The paper, published in this week's Cell, adds to a gowing body of evidence that suggests that an active life may stave off Alzheimer's.

Several epidemiological studies have suggested that education and intellectually challenging leisure activities, such as reading and playing bridge, diminish the risk of Alzheimer's dementia. Others have pointed to a possible protective role of exercise. But lower activity levels might be an early symptom of the disease, rather than an aggravating factor.

With mice, it's possible to study how environment influences the earliest stages of plaque formation. A research team led by Sam Sisodia of the University of Chicago used mice genetically engineered to develop β-amyloid plaques--extracellular protein clumps which are a key feature of Alzheimer's patients' brains--by about 4.5 months of age. When the animals were 1 month old, the researchers put nine of them in an environment amply stocked with toys and exercise equipment, and seven in standard lab cages equipped with nothing more than food, water, and bedding material.

After 5 months, the researchers killed both sets of mice and examined their brains. Animals kept in the enriched environment showed "a marked reduction in amyloid burden," Sisodia says. The decrease appeared to be related to exercise; the more time the mice had spent on running wheels, the less β-amyloid buildup. Still, Sisodia adds, other aspects of the enriched environment, such as increased visual stimuli and social interactions, could also account for the reductions.

On further study, the researchers saw increased activity of a β-amyloid--degrading enzyme called neprilysin in the brains of the busy mice, as well as changes in gene expression that could promote neuronal survival, enhance learning and memory, and increase blood vessel formation.

Zaven Khachaturian, editor of the journal Alzheimer's and Dementia, calls the work "very provocative. . . . It opens new ways of getting at the underlying mechanism" of plaque formation, he says. The findings don't match another study, however, published late 2003, which reported that enriched environments actually increase plaque formation. The reason for the discrepancy is unclear, but one reason may have been that the 2003 study used a setup that exposed mice to stress, says Gary Arendash of the University of South Florida in Tampa.

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Abstract of Cell paper