We have all been anxious before. Don't deny it. But now researchers at the University of Chicago have uncovered in mice one of the likely secrets behind the condition for some--too many copies of a certain gene. This, in turn, could yield unconventional treatments--targeted drugs that address the genetic issue, and treat anxiety as a result.
Details are published in The Journal of Clinical Investigation. Scientists got to that point by starting with previous research, which established a link in different mouse strains between anxiety-like behaviors and the Glo1 gene, which maps out the metabolic enzyme glyoxalase 1. With that in mind, the researchers injected two, 8 or 10 copies of the gene into various mouse lines. To test anxiety levels, the researchers used a number of tests. One, in particular, kept track of the time a mouse spent out in the open versus along the walls in a given space (wallflowers are more anxious, apparently).
Lo and behold, the mice with more copies of Glo1 appeared to be more anxious than those with smaller amounts. To treat it then, the scientists theorized that reducing Glo1 expression would calm the anxiety. Consider that the Glo1 gene maps out glyoxalase 1, which in turn metabolizes and then lowers cellular levels of methylglyoxal (MG). Researchers injected MG into the brain and helped make the poor anxious mice calmer as a result, all in about 10 minutes. With the knowledge that dampening the result of Glo1 expression in mice with large numbers of the gene made them calmer, scientists then tried using a small molecule inhibitor of Glo1. That also helped the mice reduce their anxiety.
There's a lot of potential benefit here. Right now, patients with anxiety take drugs that activate the GAPA-A receptor (think benzodiazepines and barbiturates). And those lead to all kinds of side effects. The researchers explain that coming up with drugs that hit the Glo1/MG interaction might be a more targeted, selective way to go in treating anxiety without the addiction or side effect problems. This may not bear out in human trials, but scientists say they want to proceed, and even view the concept as being potentially useful to treat epilepsy and sleep disorders.
"We have yet to determine if that's a better way of doing it," said senior author Abraham Palmer, a University of Chicago assistant professor of human genetics, in a prepared statement. "But it's certainly different, and it gives us a unique angle of attack on this system and potential advantages that we have yet to evaluate."
- here's the release
- read the study