Mice brainpower boosted with alteration of a single gene
"Ignorance is bliss," so the oldsaying goes, but who wouldn't give their brainpower a boost if they had thechance? By altering a single gene to inhibit the activity of an enzyme calledphosphodiesterase (PDE4B), researchers have given mice the opportunity to seewhat an increase in intelligence is like. While many people would welcome sucha 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 subjectswere dubbed Algernon by the research team conducting the study, which was ledby the University of Leeds in the UK and Mount Sinai Hospital in Toronto, butthose which had PDE4B activity inhibited were found to exhibit enhancedcognitive abilities in behavioral tests. These included a tendency to learnfaster, remember events longer and solve complex exercises better than theirordinary mice counterparts.
The researchers say that, compared to ordinarymice, the PDE4B-inhibited mice were better able to recognize another mouse theyhad been introduced to the day before and more quickly learned the location ofa hidden escape platform in the Morris water maze test.
While such abilities would likely bebeneficial to mice in the wild, the PDE4B-inhibited mice were also less likelyto recall a fearful event several days after experiencing it, and less likelyto feel anxiety, spending more time in the open and in brightly-lit spaces thanordinary mice, which prefer dark, enclosed spaces. They also exhibited lessfear response to cat urine than ordinary mice, which the researchers say couldsuggest an increase in risk-taking behavior.
However, the researchers say a diminishedmemory of fearful events could potentially be beneficial for people sufferingpost-traumatic stress disorder (PTSD) and the fact that PDE4B is also presentin humans could open avenues for treatment of the condition. However, theystress that their findings are limited to mice.
"Cognitive impairments are currently poorlytreated, so I’m excited that our work using mice has identifiedphosphodiesterase-4B as a promising target for potential new treatments,"says Dr Steve Clapcote, Lecturer in Pharmacology in the University of Leeds’ School of BiomedicalSciences, who led the study.
The researchers are now looking to develop drugs thatinhibit PDE4B that could be trialed in animals to test whether they would besuitable for clinical trials on humans. It is hoped such drugs could form thebasis of new treatments for age-related cognitive decline and disorders such asAlzheimer's disease, schizophrenia and other disorders.
"In the future, medicines targeting PDE4B maypotentially improve the lives of individuals with neurocognitive disorders andlife-impairing anxiety, and they may have a time-limited role after traumaticevents," says Dr Alexander McGirr, a psychiatrist in training at theUniversity of British Columbia, who co-led the study.
The team's study appears in the journal Neuropsychopharmacology.
Source: University of Leeds