Washington, July 17 (ANI): By uncovering how a genetic condition, called neurofibromatosis type 1, or NF1, disrupts working memory, researchers at UCLA have suggested a potential drug target for correcting learning disabilities linked with the disease.
NF1 is caused by mutations in a gene called neurofibromin, or Nf1, which makes a protein with the same name.
Previous mouse studies led by principal investigator Dr. Alcino Silva, showed that the Nf1 protein is essential for controlling the release of a neurotransmitter called GABA, which regulates brain cell activity.
Mutated versions of the protein cause too much GABA to be released, dramatically altering communication between brain cells.
In the current study, the researchers found that mice carrying Nf1 mutations showed higher levels of GABA in the brain region that regulates working memory.
The findings imply that excess GABA hinders the activity of neurons in the brain, thus interfering with working memory.
"We focused on a region of the prefrontal cortex that is critical for working memory in mice and compared it to its equivalent region in humans. When NF1 patients performed tasks that required working memory, they displayed reduced activity in the prefrontal cortex. The results were very similar to what we discovered in our mouse model," said study co-author Dr. Carrie Bearden, an associate professor of psychiatry at the Semel Institute for Neuroscience and Human Behaviour at UCLA.
The study found that as compared to healthy volunteers, the NF1 patients showed less activity in the part of the prefrontal cortex that controls working memory.
"The NF1 patients' brain cells didn't fully activate in the prefrontal cortex, as in healthy people. Patients' brain activity levels also predicted their success rate in the experiment. The less activity we saw in this brain region, the worse they performed on the tasks," said Bearden.
"Our research implies that the increased release of GABA interferes with working memory in NF1," said the study's first author, Carrie Shilyansky.
The UCLA findings suggest that learning disabilities caused by Nf1 mutations could potentially be corrected with a drug that normalizes the excess GABA's effect on brain cells.
The authors are currently studying the effect of the drug lovastatin on learning and health issues in NF1 patients.
The study is published in the latest edition of Proceedings of the National Academy of Sciences. (ANI)