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Drug Beneficial in a Model of Post-Traumatic Stress Disorder

Small molecule stabilizes a brain calcium channel

FRIDAY, Aug. 31 (HealthDay News) -- Stress-induced cognitive disorders such as post-traumatic stress disorder are associated with dysfunction in a brain calcium channel, and stabilizing the channel with a small molecule can reverse the impairment in learning and memory in mice, according to a study published in the Aug. 31 issue of Cell.

Building on previous results showing that ryanodine receptors regulate intracellular calcium levels and that stress can cause leakiness in the channel in the heart resulting in heart failure and arrhythmias, Xiaoping Liu, Ph.D., from Columbia University in New York City, and colleagues examined whether the type 2 ryanodine receptor (RyR2), which is expressed in the brain's hippocampus, had a role in stress-induced cognitive dysfunction in a mouse model.

The researchers found that the chronically-stressed mice had leaky hippocampal RyR2 channels. The mice also had impaired cognitive function, as determined by tests of hippocampal-dependent learning and memory. Both the channel leakiness and impaired cognitive function could be reversed by a small-molecule compound that stabilized RyR2 channels.

"Thus, neuronal RyR2 remodeling contributes to stress-induced cognitive dysfunction," Liu and colleagues conclude. "Leaky RyR2 could be a therapeutic target for treatment of stress-induced cognitive dysfunction."

One author is a consultant for ARMGO Pharma, which is targeting RyR channels for therapeutic purposes.

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