Health Scan: Of mice and men

Pre-clinical trial – the stage in which medications or therapies are tested on animal models – is a crucial part of drug development. This makes it possible for scientists to assess the therapeutic benefit and any side effects before the drug is administered to patients.

Prof. Ilan Golani from Tel Aviv University’s zoology department and the Sagol School for Neuroscience notes that because of their relative genetic similarity to humans, mice are most commonly used as lab animals.

Countless hours and billions of dollars have been spent on developing mouse models whose genetics can be engineered to mimic human diseases and disorders.

And while many of these models have made an invaluable contribution to the advancement of research, such as models for Parkinson’s disease and cancers, others have proven less effective.

Golani and his fellow researchers – Prof. Yoav Benjamini from the statistics and operations research department at the Sagol School of Neuroscience and Dr. Ehud Fonio from the Weizmann Institute – are contesting the viability of the models used for chronic disorders, such as the common generalized anxiety disorder (GAD). Using a hundred-fold longer experimental time-frame and comparing against wild mice, the researchers have found that the lab mice used to model chronic anxiety do not actually experience the disorder.

Instead, the behavior measured by scientists in the first minutes of an experiment is a transient response to the novel environment. With time, the mice revert back to their true temperament – calm for lab mice and anxiety for wild mice. This discovery, which has been reported in the journals PLoS One and Nature Methods, could explain why most candidate drugs developed using this mouse model have poor therapeutic value when applied to human chronic diseases, including GAD and other brain disorders, Golani says, noting that this is a well-recognized problem in the field.

A chronically anxious mouse model is crucial for testing anti-anxiety therapies, says Golani. Currently, scientists use a specific strain of lab mice thought to be particularly anxious. During experiments, they are set down into a unique environment and monitored for signs of anxiety, such as spending time in sheltered rather than exposed spaces. Once new therapies are administered, the mice are observed for a reduction in anxious behaviors.

The researchers compared the lab mouse strain used for GAD testing to a strain of first-generation wild mice born into captivity. The time frame of the experiment was extended from a few minutes through to 45 hours.

Though the lab mice appeared more anxious at first, the researchers surprisingly discovered that the lab mice settle into calm behavior while the wild mice settle into anxious behavior: “In nature, mice must always be on high alert or they will get preyed upon,” explains Golani.

In another article, the researchers call for similar scrutiny of other behavioral animal models. Should each experiment be conducted in many laboratories? It’s not necessary, Benjamini concludes.

“Developing a collaborative database that draws on the different experiments conducted across the globe, as well as appropriate data mining tools, can yield for the scientist in her isolated lab the needed yardstick to check for the replicability of her findings.

The community-based effort will help researchers screen their useful findings from questionable ones.

Going under, smiling

Children who watch a video immediately before undergoing surgery have less anxiety during inhaled anesthesia induction, the most stressful time for children throughout the peri-operative process.

Up to half of children display significant distress at the point of inhaled induction and separation from parents. Fear or exposure to a foreign environment may cause children to display high levels of distress during this time.

As a result, those who experience high levels of distress at anesthesia induction may have more pain during recovery, The research study was conducted by student Katerine Mifflin of Dalhousie University in Halifax, Nova Scotia, under the supervision of Profs. Jill Chorney and Thomas Hackman.

“Our study is one of the first to examine the effectiveness of video to reduce anxiety in children undergoing inhaled induction,” says Chorney.

“On the basis of the previous research with cartoon and video use in minor medical procedures, it was expected that playing a video clip during anesthesia induction would be effective at reducing anxiety.”

“The 97 study participants were assigned to either the experimental video distraction group or control group,” says Chorney.

“Participants in the video distraction group were presented with a list of age-appropriate videos to choose from, asked what they enjoyed viewing at home and a similar clip was found on YouTube for the child to view during induction. Enabling the participant to choose a video allowed for parental approval of the video and gave the child the opportunity to become familiar with the content, thus becoming engaged with the distractor and possibly avoiding anticipatory anxiety.”