{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:18:39Z","timestamp":1768519119559,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,4]]},"group-title":"Neuroscience","reference-count":15,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Excessive alcohol use damages the brain, especially corticolimbic regions such as the hippocampus and rhinal cortices, leading to learning and memory problems. While neuroimmune reactivity is hypothesized to underly alcohol-induced damage, direct evidence of the causative role of microglia, brain-resident immune cells, in this process is lacking. Here, we depleted microglia using PLX5622 (PLX), a CSF1R inhibitor commonly used in mice, but rarely in rats, and assessed cell death following binge-like alcohol exposure in male rats. Eleven days of PLX treatment depleted microglia &gt;90%. Further, PLX treatment prevented alcohol-induced neuronal death in the hippocampus and rhinal cortices, as the number of FluoroJade-B-positive cells (dying neurons) was reduced to control diet levels. This study provides direct evidence that alcohol-induced microglial reactivity is neurotoxic in male rats. Improved understanding of alcohol-microglia interactions is essential for developing therapeutics that suppress pro-cytotoxic and\/or amplify protective microglia activity to relieve alcohol-related damage.<\/jats:p>","DOI":"10.1101\/2024.11.04.621917","type":"posted-content","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T21:10:16Z","timestamp":1730754616000},"source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological depletion of microglia protects against alcohol-induced corticolimbic neurodegeneration during intoxication in male rats"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6638-6378","authenticated-orcid":false,"given":"Erika R.","family":"Carlson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer K.","family":"Melbourne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3466-9912","authenticated-orcid":false,"given":"Kimberly","family":"Nixon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024110803150969000_2024.11.04.621917v1.1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1678-y"},{"key":"2024110803150969000_2024.11.04.621917v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801284-0.00010-5"},{"key":"2024110803150969000_2024.11.04.621917v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2018.12.007"},{"key":"2024110803150969000_2024.11.04.621917v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.07.001"},{"key":"2024110803150969000_2024.11.04.621917v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.11.017"},{"key":"2024110803150969000_2024.11.04.621917v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.09.019"},{"key":"2024110803150969000_2024.11.04.621917v1.7","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01972-5"},{"key":"2024110803150969000_2024.11.04.621917v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.12.016"},{"key":"2024110803150969000_2024.11.04.621917v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2019.06.011"},{"key":"2024110803150969000_2024.11.04.621917v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2017.02.175"},{"key":"2024110803150969000_2024.11.04.621917v1.11","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-5"},{"key":"2024110803150969000_2024.11.04.621917v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2019.100010"},{"key":"2024110803150969000_2024.11.04.621917v1.13","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0856-z"},{"key":"2024110803150969000_2024.11.04.621917v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.05.011"},{"key":"2024110803150969000_2024.11.04.621917v1.15","first-page":"183","article-title":"Alcohol\u2019s Effects on the Brain: Neuroimaging Results in Humans and Animal Models","volume":"38","year":"2017","journal-title":"Alcohol Research: Current Reviews"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.11.04.621917","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:23:55Z","timestamp":1768461835000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.11.04.621917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":15,"URL":"https:\/\/doi.org\/10.1101\/2024.11.04.621917","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1007\/s11481-025-10173-x","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,11,4]]},"subtype":"preprint"}}