Alcohol use disorders (AUDs) affect millions of people and cause a large economic burden for society. Despite how common AUDs are, they are not completely understood and are difficult to treat. Recent research supports a role for immune signaling in the development of AUDs, the molecular changes that make it difficult to quit, and the brain damage that results from chronic alcohol use. Pharmacological studies and genetic manipulation experiments suggest that neuroimmune signaling could be a therapeutic target in the treatment of AUDs. However, there are important aspects of neuroimmune signaling that are not well understood and serve as a barrier to the development of treatments that target these pathways. These barriers include a lack of knowledge about the role of microglia and other central nervous system cell types in neuroimmune signaling. The proposed research will investigate the role of microglia and neuroimmune signaling in the response to chronic ethanol consumption.
The first aim will use RNA sequencing to identify gene expression changes in microglia following chronic ethanol consumption.
The second aim will characterize the cell type localization of neuroimmune signaling in the brain under control and ethanol treated conditions as well as evaluate changes in immune protein signaling and localization in response to chronic ethanol consumption. This study will provide important information about the changes that occur in microglia following chronic ethanol consumption, which will help to elucidate the neuroimmune signaling process. The RNA sequencing data from Aim 1 will identify microglial gene networks that respond to ethanol, revealing potential networks to target in the treatment of AUDs. This study will also provide important information about the cell type localization of immune signaling, which is important in designing future experiments and developing treatments. These findings will not only have relevance in the field of addiction, but also for the many other neurological conditions that involve neuroimmune signaling, such as ischemia, Alzheimer's Disease, Multiple sclerosis, Parkinson's disease, and traumatic brain injury. Understanding this signaling process common to these diseases provides an opportunity for developing therapeutic agents with that will work in the treatment of multiple conditions.
Recent evidence suggests that immune signaling in the brain plays a key role in the development of alcoholism. This project will investigate the role of microglia and immune signaling in the response to chronic alcohol consumption. Results of the proposed research will help to better understand the mechanisms underlying alcohol addiction and develop better treatments.
| McCarthy, Gizelle M; Warden, Anna S; Bridges, Courtney R et al. (2018) Chronic ethanol consumption: role of TLR3/TRIF-dependent signaling. Addict Biol 23:889-903 |
| McCarthy, Gizelle M; Farris, Sean P; Blednov, Yuri A et al. (2018) Microglial-specific transcriptome changes following chronic alcohol consumption. Neuropharmacology 128:416-424 |
| Warden, Anna; Erickson, Emma; Robinson, Gizelle et al. (2016) The neuroimmune transcriptome and alcohol dependence: potential for targeted therapies. Pharmacogenomics 17:2081-2096 |
