Researchers have created unusually intelligent mice by altering a single gene.
The researchers, led by scientists at the University of Leeds in England and Mount Sinai Hospital in Toronto, say their research sheds light on the molecular underpinnings of learning and memory. This could lead to research into new treatments for age-related cognitive decline, cognitive disorders such as Alzheimer’s disease and schizophrenia, as well as other conditions, they say.
The gene the researchers altered inhibits the activity of an enzyme called phosphodiesterase-4B (PDE4B), which is present in many organs, including the brain.
“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 Dr. Steve Clapcote, a lecturer in pharmacology in the University of Leeds’ School of Biomedical Sciences, who led the study.
The study found that the altered mice showed enhanced cognitive abilities. They tended to learn faster, remember events longer and solve complex exercises better than ordinary mice.
For example, the “brainy mice” showed a better ability than ordinary mice to recognize another mouse they had been introduced to the day before, the researchers report. They were also quicker at learning the location of a hidden escape platform in a test called the Morris water maze.
However, the brainy mice also showed less recall of a fearful event after several days than ordinary mice, the researchers found.
While the study was limited to mice, the researchers noted that PDE4B is present in humans. The diminished memory of fear among these mice could be of interest to researchers looking for treatments for pathological fear, such as post-traumatic stress disorder (PTSD), the researchers said.
The altered mice also showed less anxiety, according to the findings. They spent more time in open, brightly lit spaces than ordinary mice, which preferred dark, enclosed spaces.
And while ordinary mice are naturally fearful of cats, the altered mice showed a decreased fear response to cat urine, suggesting that one effect of inhibiting PDE4B could be an increase in risk-taking behavior, the researchers said.
So, while the altered mice excelled at solving complex exercises, their low levels of anxiety could be counterproductive for a wild mouse, the researchers add.
The researchers are now working on developing drugs that will inhibit PDE4B. These drugs will be tested in animals to see whether any would be suitable for clinical trials in humans, they 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,” said Dr. Alexander McGirr, a psychiatrist in training at the University of British Columbia, who co-led the study.
Source: The University of Leeds