{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T01:13:19Z","timestamp":1774055599804,"version":"3.50.1"},"reference-count":104,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by mutation or loss of\n                      <jats:italic>UBE3A<\/jats:italic>\n                      and marked by intellectual disability, ataxia, autism\u2010like symptoms, and other atypical behaviors. One route to treatment may lie in the role that environment plays early in postnatal life. Environmental enrichment (EE) is one manipulation that has shown therapeutic potential in preclinical models of many brain disorders, including neurodevelopmental disorders. Here, we examined whether postweaning EE can rescue behavioral phenotypes in\n                      <jats:italic>Ube3a<\/jats:italic>\n                      maternal deletion mice (AS mice), and whether any improvements are sex\u2010dependent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male and female mice (C57BL\/6J\n                      <jats:italic>\n                        Ube3a\n                        <jats:sup>tm1Alb<\/jats:sup>\n                      <\/jats:italic>\n                      mice and wild\u2010type (WT) littermates; \u226510 mice\/group) were randomly assigned to standard housing (SH) or EE at weaning. EE had a larger footprint, a running wheel, and a variety of toys that promoted foraging, burrowing, and climbing. Following 6\u00a0weeks of EE, animals were submitted to a battery of tests that reliably elicit behavioral deficits in AS mice, including rotarod, open field, marble burying, and forced swim; weights were also monitored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In male AS\u2010EE mice, we found complete restoration of motor coordination, marble burying, and forced swim behavior to the level of WT\u2010SH mice. We also observed a complete normalization of exploratory distance traveled in the open field, but we found no rescue of vertical behavior or center time. AS\u2010EE mice also had weights comparable to WT\u2010SH mice. Intriguingly, in the female AS\u2010EE mice, we found a failure of EE to rescue the same behavioral deficits relative to female WT\u2010SH mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Environmental enrichment is an effective route to correcting the most penetrant phenotypes in male AS mice but not female AS mice. This finding has important implications for the translatability of early behavioral intervention for AS patients, most importantly the potential dependency of treatment response on sex.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2468","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T02:47:15Z","timestamp":1641350835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sex\u2010dependent influence of postweaning environmental enrichment in Angelman syndrome model mice"],"prefix":"10.1002","volume":"12","author":[{"given":"Jameson A.","family":"Cosgrove","sequence":"first","affiliation":[{"name":"Department of Biology Augustana University  2001 S. Summit Avenue Sioux Falls South Dakota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren K.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Biology Augustana University  2001 S. Summit Avenue Sioux Falls South Dakota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Kiffmeyer","sequence":"additional","affiliation":[{"name":"Department of Biology Augustana University  2001 S. Summit Avenue Sioux Falls South Dakota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8119-1213","authenticated-orcid":false,"given":"Alexander D.","family":"Kloth","sequence":"additional","affiliation":[{"name":"Department of Biology Augustana University  2001 S. 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