In a second set of experiments, the team also showed that chemically inhibiting the ASIC1a protein in normal mice (using a component of tarantula venom) similarly blunted the innate fear response.
"Showing that pharmacologically blocking the channel reduces innate fear behavior, in theory, sets the stage for investigating whether therapies that block these ion channels in humans might be effective in anxiety disorders," said Wemmie, who also is a physician and researcher at the Veterans Affairs (VA) Iowa City Health Care System.
The UI team found that ASIC1a is concentrated in brain regions that are critical for fear behaviors and responses, including the amygdala and an area called the bed nucleus of the stria terminalis (BNST), which is thought to be particularly important for innate fear behaviors. The study also shows that mice without ASIC1a have altered neuronal activity in these fear circuit structures.
The researchers speculate that because the gene is localized to brain regions involved in fear, targeting the ASIC1a protein might have a more focused effect on anxiety with fewer side effects than existing treatments, which affect systems throughout the brain, not just those involved in the fear response.
"Current treatments for anxiety have problems such as risk of addiction, slow onset of action and other types of side effects that make people not want to take them," Wemmie explained. "If we could find something that was more specific, or even had a different set of side effects, that could be an advantage."
Although this study examined the effect of disrupting the ion channel in mice, the mouse gene is very similar to the human gene, and the ASIC1a is present in human brains, where it i
Contact: Jennifer Brown
University of Iowa