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Anthocyanins are naturally occurring compounds abundant in blueberries and in other red fruits which have been shown to be successful in the treatment of several neurological diseases, at least in in vitro and in vivo disease models. The aim of the present work was to study the ability of an anthocyanin-rich extract (ARE) obtained from Portuguese blueberries to alleviate autism-like symptoms in a valproic acid (VPA) mouse model of ASD and to get insights into the underlying molecular mechanisms of such benefits. Therefore, pregnant BALB\/c females were treated subcutaneously with a single dose of VPA (500 mg\/kg) or saline on gestational day 12.5. Male offspring mice were orally treated with the ARE from Portuguese blueberries (30 mg\/kg\/day) or the vehicle for three weeks, and further subjected to behavioral tests and biochemical analysis. Our data suggested that the ARE treatment alleviated autism-like behaviors in in utero VPA-exposed mice and, at the same time, decreased both neuroinflammation and gut inflammation, modulated the gut microbiota composition, increased serotonin levels in cerebral prefrontal cortex and gut, and reduced the synaptic dysfunction verified in autistic mice. Overall, our work suggests that anthocyanins extracted from Portuguese blueberries could constitute an effective strategy to ameliorate typical autistic behaviors through modulation of the microbiota\u2013gut\u2013brain axis.<\/jats:p>","DOI":"10.3390\/ijms23169259","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T21:23:56Z","timestamp":1660771436000},"page":"9259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Attenuation of Autism-like Behaviors by an Anthocyanin-Rich Extract from Portuguese Blueberries via Microbiota\u2013Gut\u2013Brain Axis Modulation in a Valproic Acid Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-0281","authenticated-orcid":false,"given":"Diana","family":"Serra","sequence":"first","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"CIVG\u2014Vasco da Gama Research Center, EUVG\u2014Vasco da Gama University School, 3020-210 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-7988","authenticated-orcid":false,"given":"Joana F.","family":"Henriques","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7847-5063","authenticated-orcid":false,"given":"F\u00e1bio J.","family":"Sousa","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Mariana","family":"Laranjo","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"PhD Program in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0504-5756","authenticated-orcid":false,"given":"Rosa","family":"Resende","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8740-6411","authenticated-orcid":false,"given":"Marisa","family":"Ferreira-Marques","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Victor","family":"de Freitas","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV\u2014Research Unit, Faculty of Science, Porto University, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-8540","authenticated-orcid":false,"given":"Gabriela","family":"Silva","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Jo\u00e3o","family":"Pe\u00e7a","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Department of Life Science, Faculty of Science and Technology, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Teresa C. P.","family":"Dinis","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Leonor M.","family":"Almeida","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3004-531 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.pharmthera.2018.05.007","article-title":"Autism Spectrum Disorder: Classification, diagnosis and therapy","volume":"190","author":"Sharma","year":"2018","journal-title":"Pharmacol. 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