Treatment reduces anxiety and memory loss in mice, shows potential for human use

Researchers believe they may have uncovered a potential breakthrough for treating memory, anxiety, and fear disorders in humans— all thanks to altering a single gene in mice.

The gene was changed to inhibit the activity of an enzyme called phosphodiesterase-4B (PDE4B)—an enzyme present in the brain as well as other organs in both mice and humans.

The mice with the inhibited PDE4B showed enhanced cognitive abilities when compared to unaltered mice; they tended to learn faster, have a better memory, and be more adapt at solving complex puzzles. For example, when the “smart” mice were introduced to another mouse, they were better at recognizing it a day later, and they were quicker to find hidden underwater platforms in Morris tests.

Even more interesting was what the mice suddenly lacked. The “smart” mice showed less recall of fearful events after several days elapsed and appeared less anxious in general—they spent more time in open, brightly-lit spaces than the regular mice (who typically prefer dark, enclosed spaces). Further, when presented with cat urine, the PDE4B mice were less fearful than the normal mice.

This seems to indicate that, along with altering learning and memory, the inhibition of the enzyme PDE4B also decreases fear and anxiety while increasing risk-taking behavior. This would be counterproductive in a wild mouse, for sure—but probably not so much in humans.

Potential for human usage

In a press release, Dr. Alexander McGirr, a psychiatrist in training at the University of British Columbia and co-leader of the study, said, “In the future, medicines targeting PDE4B may potentially improve the lives of individuals with neurocognitive disorders and life-impairing anxiety, and they may have a time-limited role after traumatic events.”

Dr Laura Phipps of Alzheimer’s Research UK, who were not involved in the study, added, “This study highlights a potentially important role for the PDE4B gene in learning and memory in mice, but further studies will be needed to know whether the findings could have implications for Alzheimer’s disease or other degenerative mental conditions. We’d need to see how this gene could influence memory and thinking in people to get a better idea of whether it could hold potential as a target to treat Alzheimer’s.

“There is currently a lack of effective treatments for dementia and understanding the effect of genes can be a key early step on the road to developing new drugs. With so many people affected by dementia, it is important that there is research into a wide array of treatment approaches to have the best chance of helping people sooner.”

The study is published in Neuropsychopharmacology.


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