Scientists have created super-intelligent mice that are less anxious and fearful by genetically modifying an enzyme called phosphodiesterase-4B (PDE4B). The researchers say the brainy mice could provide the basis into new treatments of cognitive disorders such as Alzheimer's and schizophrenia.
PDE4B is present in many organs of vertebrate bodies – including the brain. The scientists from the University of Leeds inhibited its activity and found that in behavioural tests, the mice showed enhanced cognitive abilities. They could learn faster, remember events for longer and solve complex exercise far faster than normal mice. The intelligent mice could better recognise another mice they had been introduced to a day earlier and they were faster at learning the location of a secret escape platform in a water maze.
Rhe clever mice also showed less recall of a fearful event in the days following and showed less anxiety in general – they tended to spend more time in open, brightly-lit spaces compared to the normal nice, which opted for dark enclosed spaces. Interestingly, the PDE4B inhibited mice were also less scared of cats, showing a decreased fear response to cat urine than normal. This, they say, could have an adverse effect in the wild.
Scientists say these findings could be of interest to researchers looking at treatments for PTSD and pathological fear. Published in the journal Neuropsychopharmacology, they authors concluded: "Our data establish specific inhibition of PDE4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory.
The authors now plan to develop drugs that specifically inhibit the enzyme and will test them on animals to see if any could be suitable for clinical trials in humans. Alexander McGirr, who co-led 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."
Study leader Steve Clapcote added: "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."
Laura Phipps of Alzheimer's Research UK commented on the study: "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."