New research suggests that mental stimulation and exercise, at least in mice, might delay the onset of Huntington's disease symptoms. Mental gymnastics, while not providing a cure, does seem to help the brain develop fast enough to mask or offset the irreversible and fatal cell-degeneration characteristic of this devastating inherited condition, announce Anton van Dellen and colleagues from the University of Oxford, UK.

This is the first experimental demonstration that environment plays a large part in the progress of Huntington's disease, altering the behaviour of the mice and even the structure of their brains. According to another study in Nature Medicine1, environmental enrichment also appears to help rats recovering from brain damage, and several surveys hint that degenerative diseases such as Huntington's progress more slowly in better educated people.

The exact sequence of mutated DNA responsible for Huntington's disease has been known since 1993. Soon after it was discovered, a strain of mice was engineered with a very similar mutation. These mice display Huntington's symptoms, but obviously on a far shorter timescale.

Van Dellen's group investigated whether the surroundings that Huntington's disease (HD) mice experience as they grow have any effect on the condition. They put baby 'transgenic' HD mice and healthy mice in two different environments: one basic and functional, and the other an assault course of ever-changing colourful objects for the rodents to explore.

As they report in Nature2, the researchers monitored the progress of the disease as they mice grew up, with some simple tests of coordination. For example, the mice were placed at the end of a narrow rod, as a test of balance and dexterity.

Whereas healthy mice immediately turn around and run back along the rod, at the end of 22 weeks, none of the HD mice reared in the sparse environment was able to turn. But just one of the animals exposed to the enriched environment failed the test.

Furthermore, by the end of the study the size of the cerebral cortex - the part of the brain involved with motor coordination and high-level processing - was 13% larger in the 'busy' HD mice than in the 'bored' HD mice. Although all brains of the HD mice showed clear signs that the disease had set in, the stimulating environment seemed to have slowed its progress significantly. "We were surprised at how dramatic these results were," comments team member Anthony Hannan.

The team do not yet know exactly what caused this slowing of the disease. But they suggest that the greater sensory input and physical activity may have made the cortex develop faster and even grow larger than if it were left unstimulated -- the 'use it or lose it' theory. Further studies will focus on the changes occurring at the cellular level in stimulated brains, which the researchers hope will shed light on the matter.

Whether these results will bring new therapies to human sufferers is uncertain. The effect of the environment on the brains of the HD mice was pronounced, giving hope of a similar process in humans. But nobody spends their life in conditions as sparse as the empty cages of the mice, so it is difficult to see how peoples' 'mental and physical stimulation' could be increased. As Hannan cautions, "we view [our results] as a start, but we don't want to give a false hope -- this is an extremely serious disease." One recent ray of hope for Huntington's is the finding, reported in Cell3, that if the mutated gene is deactivated in HD mice, some of their brain damage is reversed and the mice make an impressive recovery.