Enhanced environment restores memory in mice with neurode...( ks after the induction of p25. At this ...)

The researchers engineered mice so that they could switch the p25 transgene on at will. Activation of p25 has been implicated in a variety of neurodegenerative diseases. Once activated in the mice, the p25 transgene produces neural pathology very similar to that of patients with Alzheimer's disease, said Tsai. The animals show brain atrophy and loss of neurons due to the same kind of cellular abnormalities seen in people who have Alzheimer's disease, she said.

Researchers have long known that an environment rich in sensory stimuli can improve learning in mice. So, Tsai and her colleagues decided to explore whether such an environment could improve learning and memory in their mice after a large number of neurons were already lost.

In their experiments, they switched on p25 in older mice. The genetic change induced brain atrophy and neuronal loss. They then used two tests to assess learning and memory in these older mice. In the "fear-conditioning" test, the animals were required to learn to associate a specific chamber with a mild electric shock. The second test required the animals to learn to find a submerged platform in a tank of murky water.

The researchers placed some of the animals in a large chamber with a variety of stimuli: an exercise treadmill, colorful toys with various shapes and textures that were changed daily, and other mice. Their experiments showed that animals with neurodegeneration due to p25 activation had significant gains in learning and memory when they were exposed to this enriched environment. Those animals fared better on memory tests than the animals that remained in standard cages.

The researchers also tested the effects of an enriched environment on the animals' long-
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
29-Apr-2007