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Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12\u201314 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number\u00a0of\u00a0aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and\/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.<\/jats:p>","DOI":"10.1038\/s41598-018-24741-0","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T08:53:21Z","timestamp":1524041601000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-248X","authenticated-orcid":false,"given":"Ann","family":"Van der Jeugd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-060X","authenticated-orcid":false,"given":"Arnaldo","family":"Parra-Damas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Baeta-Corral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M.","family":"Soto-Fagu\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"LaFerla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Gim\u00e9nez-Llort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"D\u2019Hooge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Saura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,24]]},"reference":[{"key":"24741_CR1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/j.neuron.2014.05.004","volume":"82","author":"TL Spires-Jones","year":"2014","unstructured":"Spires-Jones, T. 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