Grant: Operating Grant

Each year, millions of patients undergo general anesthesia worldwide. It is widely assumed that brain function rapidly returns to baseline after the anesthetics are eliminated from the body. However, many patients experience debilitating long-term cognitive deficits, especially memory loss after anesthesia and surgery. Such memory loss is associated with poor long-term outcomes including loss of independence, premature retirement and increased mortality. Our published results from studies of laboratory animals show that anesthetics trigger a sustained hyperactivity of "memory-blocking" receptors in the brain and this hyperactivity causes memory loss. The goal of this grant is to understand the underlying molecular mechanisms and develop strategies to prevent such memory loss. Our exciting preliminary results suggest that astrocytes, which are the most abundant "support" cells in the brain, play a central role. Astrocytes appear to release soluble factors that increase the activity of memory-blocking receptors in neurons. The studies proposed in this application will identify these soluble factors and prevent their release with a novel drug treatment. We will also determine whether memory can be restored with an inhibitory peptide that reduces the hyperactivity of memory-blocking receptors. These results will increase our understanding of how astrocytes contribute to memory processes and the cause of postanesthetic memory loss. Further, new knowledge gained from these studies will have broad implications for a variety of memory-related disorders.