Environmental enrichment lessens protein deficits in mouse model of Huntington’s disease

Staying physically or mentally active can slow down chemical changes in the brain that lead to the neurodegeneration of Huntington’s disease, researchers show in a mouse model of the disorder.

Levels of brain-derived neurotrophic factor (BDNF) stop declining when Huntington’s disease transgenic mice are housed in an enriched environment, the scientists say. BDNF promotes neuron growth and survival and can also regulate communication between neurons.

“The finding that environmental enrichment increases BDNF, and that this slows disease progression, provides a potential mechanism for the effects of environmental enrichment on Huntington’s disease,” says M. Flint Beal, chair of neurology at Cornell University Medical College in New York.

The new study appears in the March 3 issue of The Journal of Neuroscience and was supported by the U.K. Medical Research Council.

Huntington’s disease is a genetic brain disorder that usually strikes in midlife. As the disease progresses, patients experience involuntary dancelike movements called chorea, as well as cognitive decline. Currently, there are no effective treatments, and patients with the disease usually die 10 to 20 years after onset. The disorder affects approximately 30,000 Americans.

In the study, enriched mice had play objects placed in their cages that changed every two days, such as small, open, wooden boxes and cylindrical cardboard tunnels. To measure motor symptoms, the researchers placed five-month-old enriched and nonenriched mice on the central cylinder of a rotarod apparatus. The cylinder rotated, slowly at first, then accelerating. The amount of time a mouse remained on the rotating rod was a measure of Huntington’s disease-associated motor symptoms.

In transgenic mice housed without enrichment, BDNF protein levels declined, but in mice housed in enriched conditions, the levels remained normal. Enriched mice also showed fewer Huntington’s disease-like motor symptoms.

“The study offers hope for the clinical treatment of Huntington’s disease,” says primary author Tara Spires of the Physiology Department at the University of Oxford, Oxford, U.K. “Enhanced physical and mental activity have been associated with reduced risks of dementia due to Alzheimer’s disease. These new data demonstrate a mechanism by which such environmental factors may slow down chemical changes in the brain that cause Huntington’s disease as well.”

Spires’ coauthors include Helen E. Grote, Neelash K. Varshney, Patricia M. Cordery, Anton van Dellen, Colin Blakemore, and Anthony J. Hannan. The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 34,000 basic scientists and clinicians who study the brain and nervous system. Spires can be reached via e-mail at: tspires@partners.org.