(Great Neck, N.Y. - May 26, 2009) — A brain protein involved in fear behavior and anxiety may represent a new target for depression therapies, according to a report in the April 29th Journal of Neuroscience about research by NARSAD Investigator John Wemmie, M.D., Ph.D., and colleagues.
Dr. Wemmie’s team at the University of Iowa and the Iowa City Veterans Affairs Medical Center, along with collaborators from the University of Memphis and the University of Utah, found that disrupting ASIC1a, an ion channel protein in the brain, produced an antidepressant-like effect in mice similar to that produced by currently available antidepressant drugs. Importantly, the study also showed that ASIC1a's effect arose through a new and different biological mechanism.
"The mechanism issue is important because if a patient doesn't respond to one drug, the chances of them responding to another drug that works through the same mechanism are low," said Dr. Wemmie, who received NARSAD Young Investigator awards in 2004 and 2007. "We need antidepressants with new mechanisms of action to help those people who don't respond to what is currently available."
The results suggest that ASIC1a inhibition represents a new approach to antidepressant therapy. The channel can be blocked pharmacologically. In addition, manipulating brain pH (a measure of acidity) might be used to inhibit this ion channel, which is activated by acid (low pH). The study also pointed to the potential efficacy of using antidepressant drugs and inhibiting ASIC1a simultaneously.
The researchers focused on ASIC1a because recent studies have pointed to a role for this ion channel in depression. In particular, previous animal studies from Dr. Wemmie's lab showed that ASIC1a plays an important role in fear responses (panic) and anxiety, conditions that often accompany depression. Other research has suggested a strong relationship between anxiety, depression and the brain's fear circuitry, including the amygdala, where ASIC1a is abundant.
In their latest study, Dr. Wemmie's team used experiments targeting the amygdala to show that this brain region is a key site of action for ASIC1a's antidepressant effect.