Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents.
Robert Adron HarrisMichal BajoRichard L BellYuri A BlednovFlorence P VarodayanJay M TruittGiordano de GuglielmoAmy W LasekMarian L LogripLeandro F VendruscoloAmanda J RobertsEdward RobertsOlivier GeorgeJody MayfieldTimothy R BilliarDavid J HackamR Dayne MayfieldGeorge F KoobMarisa RobertoGregg E HomanicsPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
Toll-like receptor 4 (TLR4) is a key mediator of innate immune signaling and has been implicated in alcohol responses in animal models and human alcoholics. Members of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium participated in the first comprehensive study across multiple laboratories to test the hypothesis that TLR4 regulates excessive alcohol consumption in different species and different models of chronic, dependence-driven, and binge-like drinking. Although TLR4 was not a critical determinant of excessive drinking, it was important in the acute sedative effects of alcohol. Current research efforts are directed at determining which neuroimmune pathways mediate excessive alcohol drinking and these findings will help to prioritize relevant pathways and potential therapeutic targets.
Keyphrases
- alcohol consumption
- toll like receptor
- inflammatory response
- nuclear factor
- immune response
- weight gain
- innate immune
- quality improvement
- endothelial cells
- liver failure
- respiratory failure
- genome wide
- drug induced
- gene expression
- intensive care unit
- pluripotent stem cells
- induced pluripotent stem cells
- extracorporeal membrane oxygenation
- mechanical ventilation