Mice genetically made smarter and less anxious

Researchers have created mice with superior intelligence by altering a single gene. The study could shed new light onto our understanding of learning and memory functions, with potential applications in the treatment of age-related cognitive decline.

Researchers inhibited the PDE4B enzyme in mice to make them smarter and less fearful (credit: Getty).

Researchers inhibited the PDE4B enzyme in mice to make them smarter and less fearful (credit: Getty).

The results of the study were published last week in the journal Neuropsychopharmacology. The team of researchers altered a gene in the target mice to inhibit a specific enzyme called phosphodiesterase-4B (PDE4B), which is present in many organs including the brain. Upon inhibition of PDE4B, the mice showed enhanced cognitive abilities – namely, they became faster at learning, they could remember events for longer and perform complex exercises better than a control group of ordinary mice.

For instance, the “smarter” mice could recognize more easily other mice they had been introduced to the day before and they were faster at learning the location of a hidden exit in the Morris water maze test (the rat is placed in a large circular pool and is supposed to find, based on certain cues, an invisible or visible platform that would allow it to escape).

The PDE4B-inhibited mice also showed less recall of a fearful event after several days than ordinary mice. They displayed less anxiety and seemed to like spending more time in open and brightly-lit environments in comparison with ordinary mice which instead preferred dark and enclosed spaces. However, the researchers reported that the PDE4B-inhibited mice showed decreased fear response to cat urine, which they associated with increased risk-taking behaviour.

These interesting results open new directions of research. The PDE4B enzyme is present in humans, and although human testing has not yet been performed, the findings raise the future possibility of using PDE4B-inhibiting drugs to cure pathological fear, of the like of post-traumatic stress disorder (PTSD), or even dementia.

The next step is, of course, developing drugs which inhibit the PDE4B enzyme and test them first onto animals and eventually on humans. “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 co-author of the study, Dr Steve Clapcote. “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,” Dr Alexander McGirr, involved in the research, added.

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Carlo Bradac

Carlo Bradac

Dr Carlo Bradac is a Research Fellow at the University of Technology, Sydney (UTS). He studied physics and engineering at the Polytechnic of Milan (Italy) where he achieved his Bachelor of Science (2004) and Master of Science (2006) in Engineering for Physics and Mathematics. During his employment experience, he worked as Application Engineer and Process Automation & Control Engineer. In 2012 he completed his PhD in Physics at Macquarie University, Sydney (Australia). He worked as a Postdoctoral Research Fellow at Sydney University and Macquarie University, before moving to UTS upon receiving the Chancellor Postdoctoral Research and DECRA Fellowships.

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