{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:03:26Z","timestamp":1768485806338,"version":"3.49.0"},"posted":{"date-parts":[[2019,12,10]]},"group-title":"Neuroscience","reference-count":60,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2019,12,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Alcohol use adversely impacts the life of millions of people worldwide. Deficits in synaptic transmission and in microglial function are common findings in human alcohol users and in animal models of alcohol intoxication. Here, we show that alcohol intake over ten consecutive days resulted in substantial loss of excitatory synapse in the prefrontal cortex, a consequence of aberrant synaptic pruning, which led to increased anxiety-like behavior. Mechanistically, these effects of alcohol intake were mediated by a detrimental increase of microglia engulfment capacity via Src-dependent activation of NFkB and consequent TNF production. Accordingly, pharmacological blockade of Src activation or TNF production by microglia, genetic ablation of TNF, or diphtheria toxin-mediated conditional ablation of microglia attenuated aberrant synaptic pruning preventing excitatory synapse loss and anxiety-like behavior. Overall, our data suggest that aberrant pruning of excitatory synapses by microglia might disrupt synaptic transmission during alcohol use.<\/jats:p>","DOI":"10.1101\/870279","type":"posted-content","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T22:55:15Z","timestamp":1576018515000},"source":"Crossref","is-referenced-by-count":0,"title":["Alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior"],"prefix":"10.64898","author":[{"given":"Renato","family":"Socodato","sequence":"first","affiliation":[]},{"given":"Joana F.","family":"Henriques","sequence":"additional","affiliation":[]},{"given":"Camila C.","family":"Portugal","sequence":"additional","affiliation":[]},{"given":"Tiago O.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Tedim-Moreira","sequence":"additional","affiliation":[]},{"given":"Renata L.","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Canedo","sequence":"additional","affiliation":[]},{"given":"C\u00e1tia","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Magalh\u00e3es","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Summavielle","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o B.","family":"Relvas","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019121203254390000_870279v1.1","first-page":"31","article-title":"Synaptic effects induced by alcohol","volume":"13","year":"2013","journal-title":"Current topics in behavioral neurosciences"},{"key":"2019121203254390000_870279v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2017.10.032"},{"issue":"1","key":"2019121203254390000_870279v1.3","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/npp.2016.121","article-title":"Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse","volume":"42","year":"2017","journal-title":"Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology"},{"issue":"4","key":"2019121203254390000_870279v1.4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/ni.3703","article-title":"Ontogeny and homeostasis of CNS myeloid cells","volume":"18","year":"2017","journal-title":"Nature immunology"},{"key":"2019121203254390000_870279v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.013"},{"key":"2019121203254390000_870279v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4397"},{"key":"2019121203254390000_870279v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14323"},{"key":"2019121203254390000_870279v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.11.017"},{"issue":"3","key":"2019121203254390000_870279v1.9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.pharmthera.2014.07.002","article-title":"Role of microglia in ethanol-induced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages","volume":"144","year":"2014","journal-title":"Pharmacology & therapeutics"},{"key":"2019121203254390000_870279v1.10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-801284-0.00001-4","article-title":"Neuroimmune mechanisms of alcohol and drug addiction","volume":"118","year":"2014","journal-title":"International review of neurobiology"},{"key":"2019121203254390000_870279v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.01.024"},{"key":"2019121203254390000_870279v1.12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.toxlet.2017.11.002","article-title":"Microglia and alcohol meet at the crossroads: Microglia as critical modulators of alcohol neurotoxicity","volume":"283","year":"2018","journal-title":"Toxicology letters"},{"issue":"18","key":"2019121203254390000_870279v1.13","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.2217\/pgs-2016-0062","article-title":"The neuroimmune transcriptome and alcohol dependence: potential for targeted therapies","volume":"17","year":"2016","journal-title":"Pharmacogenomics"},{"key":"2019121203254390000_870279v1.14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.pbb.2018.12.007","article-title":"Neuroimmune signaling in alcohol use disorder","volume":"177","year":"2019","journal-title":"Pharmacology, biochemistry, and behavior"},{"issue":"7","key":"2019121203254390000_870279v1.15","first-page":"1596","volume":"155","year":"2013","journal-title":"Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. 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