Recent studies suggest that increased acidity, or low pH, in the brain is linked to panic disorders, anxiety, and depression.
But University of Iowa neuroscientist John Wemmie, M.D., Ph.D., says his work suggests that changes in acidity are important for normal brain activity as well.
“We are interested in the idea that pH might be changing in the functional brain because we’ve been hot on the trail of receptors that are activated by low pH,” says Wemmie, an associate professor of psychiatry. “The presence of these receptors implies the possibility that low pH might be playing a signaling role in normal brain function.”
He says his studies have shown that these acid-sensing proteins are required for normal fear responses and for learning and memory in mice.
In the latest study, the first task was finding a way to measure pH changes in the brain. He teamed with Vincent Magnotta, Ph.D., UI associate professor of radiology, psychiatry, and biomedical engineering. Using Magnotta’s expertise in developing MRI (magnetic resonance imaging)-based brain imaging techniques, the researchers developed a non-invasive method to detect and monitor pH changes in living brains.
The MRI-based method was able to detect global changes in brain pH in mice, according to the researchers. Breathing carbon dioxide, which lowers pH and makes the brain more acidic, increased the signal; bicarbonate injections, which increase brain pH, decreased the MRI signal.
The method also seems to detect localized brain activity. When human volunteers viewed a flashing checkerboard — a classic experiment that activates a particular brain region involved in vision — the MRI method detected a drop in pH in that region.
The study affirms the new technique’s ability to measure pH changes in the brain, Magnotta says, giving researchers another way to study brain activity.
Currently, functional MRI (fMRI) measures brain activity by detecting a signal that’s due to oxygen levels in the blood flowing to active brain regions, but does not respond to changes in pH. The new method responds to pH changes, but is not influenced by changes in blood oxygenation, he explains.
Now that the test is in place to measure pH, the researchers plan further studies to explore how pH changes are involved in certain psychiatric diseases, including anxiety and depression.
“Brain activity is likely different in people with brain disorders, such as bipolar or depression, and that might be reflected in this measure,” Wemmie says. “And, perhaps most important at the end of the day: Could this signal be abnormal or perturbed in human psychiatric disease? And if so, it might be a target for manipulation and treatment.”
The findings were published in the latest issue of the Proceedings of the National Academy of Sciences (PNAS) Early Edition.
Source: University of Iowa Health Care