Waggoner Center Faculty, Regina Mangieri, Dayne Mayfield, Bob Messing and Yuri Blednov, are key members of the multi-disciplinary Integrative Neuroscience Initiative on Alcoholism Neuroimmune Consortium (INIA-N). Funded by the NIH, the consortium studies immune and inflammatory pathways in the brain thought to contribute to excessive drinking. INIA-N is a collaboration of ten labs from research institutions across the world investigating the hypothesis that excessive alcohol consumption produces genetic changes in immune-related pathways in the brain that promote and sustain drinking. Research conducted in the Waggoner Center is a critical component of INIA-N’s overarching plan to identify new drug targets for the treatment of Alcohol Use Disorder (AUD).
Regina Mangieri’s lab investigates the role that cytokines, proteins that help control the inflammatory pathway of the body, may play in AUD. Mangieri is researching a specific cytokine, interlukin-33, to determine if its activity is affected by alcohol consumption, and whether manipulation of this cytokine may influence alcohol intake. Mangieri notes that “neuroimmune modulators can have significant effects on the functional activity of neurons in… brain region(s) of interest” in AUD and she is extending her study of cytokines to explore how they may regulate neuronal function in the nucleus accumbens, a region important in reward-seeking and alcohol consumption.
Research in Dayne Mayfield’s lab analyzes large sets of genetic markers in individual brain cells to determine if they may be involved in excessive alcohol use. This “multi-omic” technique is incredibly powerful and Mayfield says they are “able to precisely define the role of individual types of brain cells in the context of excessive alcohol consumption”. Mayfield’s research has shown that immune signaling in glial cells serves as a key regulator of alcohol drinking. These results highlight the widespread molecular changes in the brain of individuals with AUD and greatly advance our understanding of the changes in the brain that underly the devastating impact of AUD.
Bob Messing and Yuri Blednov study the role of the enzyme phosphodiesterase 4 (PDE4) in AUD. PDE4 is another protein involved in regulating inflammatory and neuroimmune responses and has been shown to be involved in alcohol and drug dependence. This line of research is particularly exciting because previous research has revealed that PDE4 plays a role in other immune system-related inflammatory diseases, including psoriasis and psoriatic arthritis and the FDA has approved a drug, apremilast, for treatment of these diseases. Collaborative efforts of the Waggoner and INIA-N labs have shown that apremilast is also effective for reducing alcohol consumption in animal models and in humans, including humans with AUD. In addition, the Mangieri lab is testing how apremilast affects functional connectivity in brain regions involved in AUD, like the nucleus accumbans.
Participation in the INIA-N consortium is a tremendous benefit for the Waggoner Center. The research being done by the INIA-N labs has significantly advanced our understanding of the brain’s immune systems contribution to AUD and is making exciting progress identifying potential drug targets and therapies that may potentially mitigate the devastating impact of addiction-related illness.