Scientists created super-smart mice by altering a single gene in an experiment that could hold implications for the treatment of cognitive disorders in human beings.
By suppressing the activity of an enzyme known as phosphodiesterase-4B, or PDE4B, in a single gene, the researchers also found that the animals showed lower levels of anxiety and fear.
Given the links to improved intelligence and diminished anxiety, the researchers believe more research into the
workings of PDE4B enzyme may lead to treatment methods for a wide range of conditions, such as Alzheimer’s disease, age-related cognitive decline and others.
“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,” said lead author Dr. Steve Clapcote, a professor in Pharmacology in the University of Leeds’ School of Biomedical Sciences.
The researchers also surmise that targeting the PDE4B gene may give the medical community a chance to treat conditions such as post-traumatic stress disorder (PTSD), which is marked by high levels of anxiety and a heightened chance of recalling fearful events.
“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 co-author Dr. Alexander McGirr with the University of British Columbia.
The impact on humans is potentially vast.
“PDE4B is widely distributed throughout the brain in humans, monkeys and rodents, with prominent expression in the cerebral cortex” and other areas of the brain, report the researchers in the journal Neuropsychopharmacology.
After the researchers suppressed PDE4B, mice were more adept at learning and memory recall. For example, the so-called “brainy” mice were able to find a hidden escape hatch in a maze faster than non-inhibited mice. Also, the smarter mice recognized other mice faster.
“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,” said Dr. Laura Phipps of Alzheimer’s Research UK, who was not involved in the study.
“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 Phipps.
The researchers found that the PDE4B-inhibited mice show less fear, as well. They were less scared of cat urine and were more likely to be active in brightly lit spaces, as opposed to dark, small spaces that regular mice prefer.
In the future, gene therapy may someday be a realistic treatment option for individuals suffering from diseases linked to anxiety and cognitive impairment.
“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,” added Phipps.