{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:15:49Z","timestamp":1793409349871,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,11,4]],"date-time":"2009-11-04T00:00:00Z","timestamp":1257292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>\n                    Cerebral selenium (Se) deficiency is associated with neurological phenotypes including seizures and ataxia. We wanted to define whether neurons require selenoprotein expression and which selenoproteins are most important, and explore the possible pathomechanism. Therefore, we abrogated the expression of all selenoproteins in neurons by genetic inactivation of the tRNA[Ser]\n                    <jats:sup>Sec<\/jats:sup>\n                    gene. Cerebral expression of selenoproteins was significantly diminished in the mutants, and histological analysis revealed progressive neurodegeneration. Developing interneurons failed to specifically express parvalbumin (PV) in the mutants. Electrophysiological recordings, before overt cell death, showed normal excitatory transmission, but revealed spontaneous epileptiform activity consistent with seizures in the mutants. In developing cortical neuron cultures, the number of PV\n                    <jats:sup>+<\/jats:sup>\n                    neurons was reduced on combined Se and vitamin E deprivation, while other markers, such as calretinin (CR) and GAD67, remained unaffected. Because of the synergism between Se and vitamin E, we analyzed mice lacking neuronal expression of the Se\u2010dependent enzyme glutathione peroxidase 4 (GPx4). Although the number of CR\n                    <jats:sup>+<\/jats:sup>\n                    interneurons remained normal in\n                    <jats:italic>Gpx4<\/jats:italic>\n                    \u2010mutant mice, the number of PV\n                    <jats:sup>+<\/jats:sup>\n                    interneurons was reduced. Since these mice similarly exhibit seizures and ataxia, we conclude that GPx4 is a selenoenzyme modulating interneuron function and PV expression. Cerebral SE deficiency may thus act\n                    <jats:italic>via<\/jats:italic>\n                    reduced GPx4 expression.\u2014Wirth, E. K., Conrad, M., Winterer, J., Wozny, C., Carlson, B. A., Roth, S., Schmitz, D., Bornkamm, G. W., Coppola, V., Tessarollo, L., Schomburg, L., K\u00f6hrle, J., Hatfield, D. L., Schweizer, U. Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    24, 844\u2013852 (2010).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.09-143974","type":"journal-article","created":{"date-parts":[[2009,11,4]],"date-time":"2009-11-04T22:40:28Z","timestamp":1257374428000},"page":"844-852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":211,"title":["Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration"],"prefix":"10.1096","volume":"24","author":[{"given":"Eva K.","family":"Wirth","sequence":"first","affiliation":[{"name":"Neurobiology of Selenium Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Conrad","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumour Genetics Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Winterer","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Neurobiology Neuroscience Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wozny","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Neurobiology Neuroscience Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Molecular Biology of Selenium Section Laboratory of Cancer Prevention Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Roth","sequence":"additional","affiliation":[{"name":"Neurobiology of Selenium Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Neurobiology Neuroscience Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg W.","family":"Bornkamm","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumour Genetics Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Coppola","sequence":"additional","affiliation":[{"name":"Neural Development Group Mouse Cancer Genetics Program National Cancer Institute Frederick Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Tessarollo","sequence":"additional","affiliation":[{"name":"Neural Development Group Mouse Cancer Genetics Program National Cancer Institute Frederick Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Schombure","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"K\u00f6hrle","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolph L.","family":"Hateld","sequence":"additional","affiliation":[{"name":"Molecular Biology of Selenium Section Laboratory of Cancer Prevention Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Neurobiology of Selenium Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.11.3565-3576.2002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083516"},{"key":"e_1_2_6_4_1","first-page":"255","article-title":"Selenium as an integral part of factor 3 against dietary necrotic liver 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