"Ignorance is bliss," so the old saying goes, but who wouldn't give their brainpower a boost if they had the chance? By altering a single gene to inhibit the activity of an enzyme called phosphodiesterase (PDE4B), researchers have given mice the opportunity to see what an increase in intelligence is like. While many people would welcome such a treatment, the scientists say their research could lead to new treatments for those with cognitive disorders and age-related cognitive decline.
It's unclear if any of the mice subjects were dubbed Algernon by the research team conducting the study, which was led by the University of Leeds in the UK and Mount Sinai Hospital in Toronto, but those which had PDE4B activity inhibited were found to exhibit enhanced cognitive abilities in behavioral tests. These included a tendency to learn faster, remember events longer and solve complex exercises better than their ordinary mice counterparts.
The researchers say that, compared to ordinary mice, the PDE4B-inhibited mice were better able to recognize another mouse they had been introduced to the day before and more quickly learned the location of a hidden escape platform in the Morris water maze test.
While such abilities would likely be beneficial to mice in the wild, the PDE4B-inhibited mice were also less likely to recall a fearful event several days after experiencing it, and less likely to feel anxiety, spending more time in the open and in brightly-lit spaces than ordinary mice, which prefer dark, enclosed spaces. They also exhibited less fear response to cat urine than ordinary mice, which the researchers say could suggest an increase in risk-taking behavior.
However, the researchers say a diminished memory of fearful events could potentially be beneficial for people suffering post-traumatic stress disorder (PTSD) and the fact that PDE4B is also present in humans could open avenues for treatment of the condition. However, they stress that their findings are limited to mice.
"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," says Dr Steve Clapcote, Lecturer in Pharmacology in the University of Leeds’ School of Biomedical Sciences, who led the study.
The researchers are now looking to develop drugs that inhibit PDE4B that could be trialed in animals to test whether they would be suitable for clinical trials on humans. It is hoped such drugs could form the basis of new treatments for age-related cognitive decline and disorders such as Alzheimer's disease, schizophrenia and other disorders.
"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," says Dr Alexander McGirr, a psychiatrist in training at the University of British Columbia, who co-led the study.
The team's study appears in the journal Neuropsychopharmacology.
Source: University of Leeds
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