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We report here that tumor necrosis factor receptor superfamily death receptor 3 (TNFRSF25, DR3) and Fas receptors (Fas) that initiate caspase cell death cascades are increased in AUD hippocampus and following a rat adolescent binge drinking model. Death receptors are known inducers of apoptosis and cell death that recruit death domain (DD) proteins FADD and TRADD and caspases to form death-inducing signaling complexes (DISC). In postmortem human AUD hippocampus, mRNA and IHC protein are increased for the entire death receptor cascade. In AUD hippocampus, ligand\u2013death receptor pairs, i.e., TL1A-DR3 and FasL\u2013Fas, were increased, as well as FADD and TRADD, and active caspase-8, -7, -9, and caspase-3. Further,\n                    <jats:italic>p<\/jats:italic>\n                    NF\u03baB p65, a key neuroimmune transcription factor, and IL-8, a chemokine, were significantly increased. Interestingly, across AUD patients, increases in DR3 and Fas correlated with TRADD, and TRADD with active caspase+IR and IL-8+IR, consistent with coordinated activation of neuronal DISC mediated death cascades and neuroimmune gene induction in AUD. These findings support a role for DR3 and Fas neuroimmune signaling in AUD hippocampal neurodegeneration.\n                  <\/jats:p>","DOI":"10.1038\/s41380-020-0698-4","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T12:03:07Z","timestamp":1583409787000},"page":"2254-2262","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Hippocampal TNF-death receptors, caspase cell death cascades, and IL-8 in alcohol use disorder"],"prefix":"10.1038","volume":"26","author":[{"given":"Wen","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Vetreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-4976","authenticated-orcid":false,"given":"Fulton T.","family":"Crews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"698_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrn2038","volume":"8","author":"ML Block","year":"2007","unstructured":"Block ML, Zecca L, Hong JS. 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