Monday, April 30, 2007

Scientists Restore Lost Memory in Alzheimer's-Like Mice

(HealthDay News) -- In a new study, mice bioengineered to mimic the fading memory of Alzheimer's patients got their memories restored -- either by being placed in stimulating environments or by receiving a drug most commonly used to fight cancer.

While the research remains in an early stage, it "really provides hope for human patients, especially those with dementia," said study senior researcher Li-Huei Tsai, a professor of brain and cognitive sciences at the Massachusetts Institute of Technology's Picower Institute of Learning and Memory.

Her team published its findings April 29 in the online edition of the journal Nature.
Alzheimer's disease is becoming more widespread as the population ages, and five million Americans now suffer from the illness, according to the Alzheimer's Association. By 2050, unless new ways are found to prevent or treat the disease, that total could climb to 16 million.
A gradual but inexorable loss of memory is one of the tragic hallmarks of Alzheimer's disease, but neuroscientists have never been clear as to whether memories are truly lost or simply rendered inaccessible.

According to Tsai, experts have long known that a so-called "enriched" environment can boost learning. But can it also help restore fading powers of recall?

"I don't think anyone has studied this in depth, because there's only so much you can do with humans," Tsai said. "And in terms of animal models, it's been difficult, too."

However, a few years ago her team at MIT made a kind of breakthrough in that regard. They bioengineered a strain of mice that could be induced at any time in their lifespan to mimic the steady loss of brain cells -- called neurons -- that occurs with Alzheimer's and other neurodegenerative illnesses. This steady destruction of neurons can lead to serious memory deficits.

Working with this mouse model, Tsai's group first trained a number of the rodents to perform a number of tasks. They then induced an Alzheimer's-like neuronal loss that depletes memory.
However, mice that were kept in an "enriched" environment -- rooms full of shelves, perches, nesting material, tunnels and (especially) other mice -- were still able to use their memory to find their way through mazes they had learned to navigate weeks before.

In contrast, mice kept in unstimulating surroundings typically got lost and failed to complete tasks. These rodents were seemingly unable to remember tasks they had learned before, including navigating the mazes, the researchers said.

How might stimulating surroundings preserve or boost memory? "Environmental enrichment doesn't seem to be bringing back the lost neurons -- we don't think that's the case," Tsai said. "Rather, we think that environmental enrichment promotes new neurons to grow and synapses to form. We propose that it is actually rewiring the brain."

Similar results were seen when mice with induced memory loss received a new type of drug called a histone deacetylase (HDAC) inhibitor. These agents are already being used as cancer therapy and appear to work at the molecular level to "free up" genes that produce vital growth factors and proteins.

Mice given an HDAC inhibitor had much less trouble finding their way through mazes and performing other tasks that relied on memory, compared to mice that did not receive the drug, Tsai said.

Again, she believes that HDACs may have stimulated genes crucial to learning memory in the rodents' brains. This may have led to the formation of new neural networks that gave these brain-impaired mice renewed access to useful memories.

The HDAC inhibitor finding is "really intriguing," said Dr. Paul Sanberg, director of the Center of Excellence for Aging and Brain Repair at the University of South Florida College of Medicine in Tampa.

"Especially because these drugs are already being used in cancer patients, that means that they are already available clinically, so maybe they could be developed a little faster for Alzheimer's patients," he said.

Still, many questions remain. "Exactly which genes are being increased, and which are needed? I don't think that you can tell from this paper," Sanberg said.

Tsai agreed that more study is necessary before HDACs can be tested in Alzheimer's patients. "Right now, we only show the beneficial effects in animal models. Before proceeding to humans, we really have to know more," she said.

But enriched environments -- involving both mental stimulation and physical activity -- are available to help everyone's memory, right now.

"I think that's so important, and not just for Alzheimer's patients," Tsai said. "I think that all of us should keep busy and engaged. That's definitely very beneficial for everyone."

More information
There's more on Alzheimer's disease at the Alzheimer's Association.

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