BRNI Research
Memory and Neurological Disorder Modeling
Discovery of CBL-B Gene
In a study that illuminates how memory becomes impaired, the Institute recently identified a specific gene, cbl-b, which is a potential negative regulator of PKC pathways. Transgenic mice in which this gene has been knocked out had markedly enhanced long-term memory. While many such mutation-based interruptions of gene expression impair or obstruct long-term memory, none have actually significantly prolonged associative memory. Brain synapses in the hippocampus of these mice also showed new capacity to undergo facilitatory changes that can contribute to memory storage.
This cbl-b gene regulates a protein that is biochemically linked to a number of signaling pathways and inhibits the molecular pathways necessary for storing long-term memories. When the gene is deleted, these pathways are free to perform their function of transmitting memories from short- to long-term storage. These findings help identify where a breakdown in memory storage occurs, which molecular pathways are crucial to storing memories, and most importantly, the precise areas of the brain to target for further research.
Post-Traumatic Stress Disorder
To help develop drug and behavioral treatments of PTSD, models are required to more closely approximate the disorder. Unlike civilian forms of PTSD, combat-related PTSD originates in unique environments under abnormal circumstances and is often difficult to treat. Conservative estimates suggest PTSD among all veterans is three times higher than in the general population and may be as much as thirty times higher in combat veterans. Despite some progress in the diagnosis and treatment of PTSD in the general population, treatment of veterans has been less successful and is associated with an increased risk of death.
To help develop drug and behavioral treatments of PTSD there needs to be models that approximate the disorder as closely as possible. Previous models of PTSD have been based on learning theories in which the cues associated with traumatic stress are thought to remind people of and elicit reactions to the stressful event. It is upon these previous models that the less than successful treatments of combat-related PTSD have been based.
At BRNI, researchers have developed a model in which they assess the changing reactions not only to the cues associated with stress but to the stressful events themselves. It is the over-reaction to stressful events that is a hallmark of post-traumatic stress disorder and of their model. BRNI drug discovery research has also developed novel drugs that inhibit carbonic anhydrase gated attention to minimize the extended context generality that frequently accompanies the PTSD syndrome. Using this model, BRNI scientists may be able to screen drugs that could be of potential benefit to people suffering from PTSD.
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