Yale University researchers report in the Proceedings of the National Academy of Sciences (September 7-11 edition) that damage to the brain caused by chronic stress or lead poisoning can be repaired by blocking a key molecular pathway.
Research shows that rats exposed to chronic stress develop damage to the prefrontal cortex. This is an area of the brain essential to working memory, impulse control and the ability to stay focused on tasks. Long-term stress activates excessive activity of a family of enzymes called protein kinase C. As a result, there is damage to the cytoskeleton of neurons that interferes with their ability to transmit information. This failure in the brain due to stress has been associated with poor impulse control, a decline in working memory and inability to focus on tasks. These findings have a direct impact on our understanding of bipolar disorder. Genetic alterations increase protein kinase C signaling which may be linked to a loss of prefrontal grey matter and behavioral control.
Amy Arnsten, senior author and professor of neurobiology at Yale, led the team of researchers including her graduate student, Avis Brennan Hains. They blocked the action of protein kinase C in rats and as a result succeeded in stopping the effects of stress. Findings indicated that dendritic spines of neurons remained undamaged. Therefore, the rats’ ability to perform a task requiring working memory and impulse control was improved.
Arnsten explains: “When you inhibit protein kinase C, cells can talk to each other again and you rescue cognition.”
Arnsten suggests that blocking protein kinase C has potential for treating bipolar disorder and post-traumatic stress disorder. Patients with bipolar disorder have been given medications such as lithium which can inhibit protein kinase C and have proved to restore normal levels of grey matter. Moreover, she observed that such a therapy might be of assistance in reversing the effects of lead poisoning which causes learning disabilities and behavioral problems in a high number of children. Similar to the effects of stress, lead can also raise protein kinase C activity and wear down grey matter in the prefrontal cortex. These conclusions of this study imply that medications that inhibit protein kinase C may aid in restoring prefrontal brain function in children with lingering problems from lead poisoning.
Yale researchers contributing to the study: Mai Anh T. Vu, Paul K. Maciejewski, Christopher H. Van Dyck and Melissa Grotton.
The study was funded by the National Institutes of Health and the Yale Stress Center.
Proceedings of the National Academy of Sciences
Written by Stephanie Brunner (B.A.)