Blocking Brain Protein Repairs Damage Caused by Stress, Bipolar Disorder

Researchers from Yale University have discovered a way to repair damage to the brain caused by stress and how to prevent further damage from occurring.

When senior author Amy Arnsten, professor of neurobiology, and her graduate student, Avis Brennan Hains, subjected rats to chronic stress, damage occurred to the prefrontal cortex of the brain, which is “crucial to working memory, impulse control and the ability to stay focused on tasks,” according to the researchers. In addition, extended stress also caused excess production of a family of enzymes known as protein kinase C. The overproduction of these enzymes also caused damage to the cytoskeletons of neurons, hindering their ability to transmit information. When Arnsten, Hains, and the rest of the research team blocked the production of protein kinase C, the rats were protected from the effects of stress on the brain. In addition, the team also saw that “dendritic spines of neurons stayed intact and that the rats’ ability to perform a task requiring working memory and impulse control was improved.”

According to the research team, the findings of this study have “direct relevance” to the ability to understand bipolar disorder, in that “genetic insults increase protein kinase C signaling, which may be associated with a loss of prefrontal grey matter and behavioral control.” Medications like lithium can inhibit protein kinase C and thus return the levels of gray matter in the brain to normal.

In addition to protecting the brain from damage due to stress and the impact of bipolar disorder, protein kinase C inhibitors may also be beneficial for reversing the effect of lead poisoning, as excess lead can also increase levels of protein kinase C and erode grey matter.

The research team, which also included Mai Anh T. Vu, Paul K. Maciejewski, Christopher H. Van Dyck and Melissa Grotton, is hopeful that the study findings will lead to the development of medications that inhibit protein kinase C.