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Look lively

Could a busy lifestyle delay the onset of a genetic illness?

MICE that are predestined to get Huntington’s disease stay healthier for
longer when they live in a varied environment with plenty of opportunities for
exercise, climbing and exploring, neuroscientists at Oxford University have
discovered. The finding is surprising since, in people, Huntington’s is strongly
genetic, and experts had thought it unlikely to be significantly affected by
environmental factors.

“We didn’t expect this dramatic delay,” says Tony Hannan, who ran the study
with Anton van Dellen and Colin Blakemore. Reporting the findings at the
Australian Neuroscience Society meeting in Melbourne last week, Hannan said they
had expected an enriched environment to hasten the onset of the symptoms, rather
than delaying it.

“It’s enormous. It’s the first evidence that by manipulating the environment
you can delay the onset—and possibly the severity—of the disease,”
says Richard Faull, an expert in HD at the University of Auckland.

But the effects may be less dramatic in people, because “an enriched mouse is
more like a normal human”, warns Hannan.

In people with HD, brain cells die, causing them to lose control of their
movement and leading to severe cognitive and behavioural deterioration. Mice
genetically engineered to have part of the gene that causes Huntington’s get
many of these symptoms. These include a motor impairment that prevents them
turning while walking on a horizontal pole.

By the time the engineered mice in Hannan’s study were 18 weeks old, they all
fell off the pole. But when the researchers put boxes and tunnels in the cages
of similar engineered mice, and changed the box and tunnel configuration every
two days, only 15 per cent of them failed the test at the same age. They also
performed better in another test for Huntington’s symptoms.

The enriched mice also showed changes in a brain region called the striatum,
which helps to coordinate movement. More of their striatal cells contained a
protein called calbindin, which is known to protect neurons from damage.

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