Columbia University Medical Center (CUMC) researchers have identified a potential medical treatment for the cognitive effects of stress-related disorders, including post-traumatic stress disorder (PTSD). The study, conducted in a PTSD mouse model, shows that an experimental drug called S107, one of a new class of small-molecule compounds called Rycals, prevented learning and memory deficits associated with stress-related disorders. The findings were published in the online edition of Cell.

Based on his earlier work in heart and muscle disorders, Dr. Marks reasoned that chronic stress could lead to PTSD by destabilizing type 2 ryanodine receptors (RyR2) in the hippocampus, the brain region that plays a central role in learning and memory. RyR2 are channels that regulate the level of calcium in neurons, which is vital to cell survival and function.

“When we examined the hippocampal neurons of the stressed mice, we found that their RyR2 channels had become destabilized and leaky compared with channels from normal non-stressed mice which were not leaky. There was a remodeling of the channels that we had previously seen in heart and skeletal muscles from animal models of chronic diseases including heart failure and muscular dystrophy. We found these same leaky channels in samples from patients with these disorders but not in those from healthy humans,” said Dr. Marks.