Researchers are trying to understand why obesity in the 40s and 50s can lead to mental decline in the 70s. (PHOTO by Pavel Kulinich/Dreamstime/TNS)

Georgia researchers reverse mental decline in diabetic mice

Georgia researchers appear to have confirmed how obesity can erode some patients’ brain function and possibly lead to dementia.

Scientists already knew that obesity and insulin resistance in middle age appeared to be tied sometimes to cognitive decline later in life. Using genetically engineered mice, scientists at the Medical College of Georgia were able to reverse the decline.

They just revealed their findings in The Journal of Neuroscience, one of the most prestigious journals in the field. It’s too soon to say whether this will lead to a new drug to stop the problem in humans. But in the meantime, the authors do say it shows that the reasons to be healthy are more than just physical.

For people who are diabetic, insulin-resistant or gaining too much weight, “this really underscores the importance of adhering to a therapeutic regimen,” said Alexis Stranahan, an associate professor of neuroscience and the study’s principal investigator.

More than 1 million Georgians have diabetes, according to the state Department of Community Health.

The study’s results were striking: In genetically engineered mice, Stranahan’s team reversed the mental decline. She stressed the circumstances were very specific and that that doesn’t mean it can be done long-term or in humans. But it does mean they know how the mental decline can happen.

In people who are obese and insulin-resistant, the blood-brain barrier breaks down, and substances meant to stay in the blood are passing through to the nervous system. Stranahan’s team confirmed one way that happens. Or, as she says, becoming more of a gate than a barrier.

Mice share a lot of similarities with humans. When the researchers made the mice obese to the point of being insulin-resistant and diabetic, the animals lost some of their ability to find their way through a maze.

In addition, mice like to investigate new objects such as dice and golf balls (golf balls because it is Augusta, Stranahan said). When they’ve already seen an object, they’re not so interested in it anymore.

After the Augusta scientists made the mice obese, they lost their smarts: When around dice and golf balls that they’d already seen, the animals acted as if they’d never seen them before. And they’d have a harder time finding their way through a maze. That confirmed what was already known from experiments on humans a dozen years ago in Sweden, that fat in midlife can harm cognition and memory later in life.

But Stranahan’s lab did more. Science had zeroed in on a particular receptor on the blood-brain barrier as a possible cause for the trouble. Stranahan and her colleagues engineered some mice so they could shut down that receptor. When they did, the mice’s behavior returned to normal.

When it comes to this area of research, Stranahan said, “This is an exciting time.”

She also said obese patients and their doctors might want to consider that drugs may have a larger impact on obese patients’ brains.

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