Potential Novel Treatment Targets for the Cognitive Symptoms of Mental Illness Discovered

Milena Girotti, Ph.D., Expert on stress and anxiety research
Milena Girotti, Ph.D.

In a new study funded in part by the Brain & Behavior Research Foundation and conducted at the University of Texas Health Science Center at San Antonio (UTSA), researchers made a surprising discovery about how low levels of a pro-inflammatory agent in the brain may help maintain mental flexibility. Inflammation is typically associated with illness and it is known that in some cases inflammation in the brain can lead to cognitive impairment. This new research, published January 15th in The Journal of Neuroscience, could offer new insight for developing treatments for the cognitive symptoms associated with major mental illnesses such as schizophrenia, depression and post-traumatic stress disorder (PTSD).

Working with animal models, in this case both stressed and non-stressed rats, the research team, including 2012 NARSAD Young Investigator Grantee, Milena Girotti, Ph.D., Researcher and Instructor at UTSA, found that de-activating a pro-inflammatory protein (the cytokine interleukin or IL-6) in the brain made it more difficult for rats to change previously learned thoughts and behaviors when environmental changes occurred. They had thought that de-activating the protein would improve this mental processing, known as reversal learning, but to their surprise the rats were less able to adapt their previously learned behaviors. This impairment is a common cognitive symptom of many stress-related brain and behavior disorders and the new findings could offer potentially novel therapeutic targets for their treatment.

"When we started the project, we thought cognitive flexibility would be impaired by stress-induced inflammation in a region of the brain called the prefrontal cortex," said Jennifer Donegan, Professor of Pharmacology in the UTSA School of Medicine and lead author of the paper. "We decided to block interleukin-6 during stress to prevent the cognitive deficit, and to our surprise this made things worse. This suggested that it may actually be beneficial to maintain a low level of this pro-inflammatory cytokine in the brain."

Next, the research team restored a low level of IL-6 directly into the prefrontal cortex in the brains of the rats and observed improvement in the cognitive deficits. The researchers stress that these are early findings and there is much more work to do, but they are excited about the implications for potentially more effectively treating cognitive deficits.

To learn more about this research, read this press release from the UTSA.

Read the abstract of this research paper from The Journal of Neuroscience.