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Genzyme introduces new global grant program to support LSD patient community

January 10, 2016

One of the study's most novel findings concerns TLR4's important role in binge drinking. Science has traditionally considered TLR4 to be an innate immunity receptor involved with neuroinflammation in the brain. Scientists associated TLR4 with microglia, cells that support inflammatory responses in the brain. "What makes this finding particularly important for the field of neuroscience is that we're showing that TLR4 plays a significant role in neurons, specifically, the neurons that are connected to the GABA receptor," says Dr. June.

To establish the connection between the GABA receptors, TLR4 and alcohol, the scientists manipulated this pathway in the binge drinking rodents. Dr. Aurelian was a pioneer in developing a method to inhibit gene expression, helping scientists to pinpoint the role of individual genes in the body. In this study, she used a herpes viral vector ?? a deactivated herpes virus ?? to deliver a gene-modifying agent directly to the neurons in the brain, to target TLR4 and GABA receptors. The scientists found that when they artificially stimulated the GABA receptors and TLR4 in order to simulate the good feelings binge drinkers feel when drinking alcohol, the rats lost interest in alcohol for two weeks after the procedure.

Compounds exist that would stimulate the receptors in the same way the scientists did in the study. "It's very likely that, down the road, these compounds could become new therapies for binge drinking," says Dr. June. "These compounds would act like a substitute for alcohol, much like methadone acts as a substitute for heroin. They would help alcoholics stop drinking, giving them relief from their cravings and from the anxiety that they try to alleviate with drinking."

The next step is to further investigate the newly discovered role that TLR4 plays in binge drinking. Future treatments could target both GABA receptors and TLR4, or just TLR4, depending on what scientists find, according to Dr. June. More study is needed, says Dr. Aurelian: "The discovery of this involvement of TLR4 in a pathway with GABA is most remarkable. This study provides basically a totally new understanding of what TLR4 and GABA are all about. That's exciting, but there is a lot more to learn about this pathway and where it goes beyond this point. This is a fascinating new paradigm we plan to explore further."

SOURCE University of Maryland School of Medicine