‘Super-smart mice’ might help cure Alzheimer’s and schizophrenia – study

In Douglas Adams’ “Hitchhiker’s Guide to the Galaxy,” mice are the super-intelligent beings running the universe. But now human scientists – supposedly the subjects of the mice’s “complex experiments” in laboratories – can claim to be catching up.

A group of researchers from Canada and the UK have changed a single gene in the mice’s DNA to block a specific enzyme, called PDE4B, which is responsible for distributing such hormones as adrenalin in the organism, but is also allegedly connected to such pathologies as schizophrenia or manic-depressive illness.

As a result, the research team, led by Steve Clapcote, a lecturer in pharmacology at Britain's Leeds University and Alexander McGirr, a psychiatrist in training at the University of British Columbia, Canada, found out that genetically modified mice became “smarter” as well as less fearful and anxious.

The series of experiments conducted by the scientists and described in a paper published in the journal “Neuropsychopharmacology” on August 14, showed that PDE4B-inhibited “brainy” mice usually learned faster, had a better memory and were able to solve more complex tasks than normal mice.

The super-clever mice were able to recognize other mice they saw the day before and were quicker at finding and remembering the ways to get on a hidden platform by using different cues in a Morris water maze experiment, which is often used by neuroscientists to study cognitive functions.

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Additionally, they tended to be less anxious and fearful as they preferred to spend time in open brightly lit places in contrast to normal mice that usually choose dark secluded spaces. They forgot about fearful events faster and were less likely to remember them after several days. Besides, the brainy mice also showed a less startled response to cat urine, while ordinary mice are naturally afraid of cats.

Although the scientists admit that such “low-anxiety level” behavior could be counterproductive and even dangerous for wild mice, they emphasize the study has shown that inhibition of PDE4B could potentially enhance cognitive abilities as well as reduce levels of stress and anxiety.

"Our work using mice has identified phosphodiesterase-4B as a promising target for potential new treatments," said Steve Clapcote, Medical Express reported.

The experiments were limited only to mice so far but as the studied enzyme is also omnipresent in the human body and could be found particularly in the brain, these findings could be applied to treat people, the scientists believe.

"Cognitive impairments are currently poorly treated, so I'm excited that our work using mice has identified phosphodiesterase-4B as a promising target for potential new treatments," Steve Clapcote said.

Additionally, the diminished memory of fear stemming from PDE4B inhibition could pave the way for researchers trying to find a cure from pathological fears such as the Post-Traumatic Stress Disorder (PTSD).

"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," said Dr Alexander McGirr.

The research team is now working on the development of medicines aimed at specifically inhibiting PDE4B enzyme. The scientists plan to trial them on animals before starting potential clinical tests on humans.

The study's findings have already received a positive evaluation in the scientific community, as experts recognize the importance of the research, considering there's a lack of effective treatments for dementia. However, some scientists also admit that further research is needed to prove that the discovered method could really have positive implications in treating such neurodegenerative disorders as Alzheimer's.

"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 dementias. 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,” said Dr Laura Phipps of Alzheimer's Research UK, who were not involved in the study.

“Understanding the effect of genes can be a key early step on the road to developing new drugs… it is important that there is research into a wide array of treatment approaches to have the best chance of helping people sooner," she added.

Douglas Adams, whose science-fiction comic novels predicted the demise of humankind and the planned destruction of Earth by mice to make way for a new hyperspace highway, would doubtless have approved of the scientists’ work as a significant step forward in human intelligence.