{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:38:49Z","timestamp":1791092329402,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,7,23]],"date-time":"2012-07-23T00:00:00Z","timestamp":1343001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Galectins are pleiotropic carbohydrate\u2010binding lectins involved in inflammation, growth\/differentiation, and tissue remodeling. The functional role of galectins in amyotrophic lateral sclerosis (<jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>) is unknown. Expression studies revealed increases in galectin\u20101 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein in spinal cords from <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup> mice, and in galectin\u20103 and \u20109 <jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content> and proteins in spinal cords of both <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup> mice and sporadic <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> patients. As the increase in galectin\u20103 appeared in early presymptomatic stages and increased progressively through to end stage of disease in the mouse, it was selected for additional study, where it was found to be mainly expressed by microglia. Galectin\u20103 antagonists are not selective and do not readily cross the blood\u2013brain barrier; therefore, we generated <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">Gal\u20103<\/jats:styled-content>\n<jats:sup>\u2212\/\u2212<\/jats:sup> transgenic mice to evaluate galectin\u20103 deletion in a widely used mouse model of <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>. Disease progression, neurological symptoms, survival, and inflammation were assessed to determine the effect of galectin\u20103 deletion on the <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup> disease phenotype. Galectin\u20103 deletion did not change disease onset, but resulted in more rapid progression through functionally defined disease stages, more severely impaired neurological symptoms at all stages of disease, and expiration, on average, 25\u00a0days earlier than <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">Gal\u20103<\/jats:styled-content>\n<jats:sup>+\/+<\/jats:sup> cohorts. In addition, microglial staining, as well as <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, and oxidative injury were increased in <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">Gal\u20103<\/jats:styled-content>\n<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with <jats:styled-content style=\"fixed-case\">SOD1<\/jats:styled-content>\n<jats:sup>G93A<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">Gal\u20103<\/jats:styled-content>\n<jats:sup>+\/+<\/jats:sup> cohorts. These data support an important functional role for microglial galectin\u20103 in neuroinflammation during chronic neurodegenerative disease. We suggest that elevations in galectin\u20103 by microglia as disease progresses may represent a protective, anti\u2010inflammatory innate immune response to chronic motor neuron degeneration.<\/jats:p>","DOI":"10.1002\/brb3.75","type":"journal-article","created":{"date-parts":[[2012,7,23]],"date-time":"2012-07-23T07:21:13Z","timestamp":1343028073000},"page":"563-575","source":"Crossref","is-referenced-by-count":89,"title":["Deletion of galectin\u20103 exacerbates microglial activation and accelerates disease progression and demise in a <scp>SOD1<\/scp><sup>G93A<\/sup> mouse model of amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"2","author":[{"given":"Bruce J.","family":"Lerman","sequence":"first","affiliation":[{"name":"Department of Pharmacology George Washington University School of Medicine and Health Sciences  Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Integrative Systems Biology George Washington University School of Medicine and Health Sciences  Washington DC"},{"name":"Department of Pediatrics and Center for Genetic Medicine Children's National Medical Center  Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"NINDS, Neurodegeneration Cluster National Institutes of Health  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Bouri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Center for Genetic Medicine Children's National Medical Center  Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel K.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of California Davis School of Medicine  Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu\u2010Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of California Davis School of Medicine  Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Rothstein","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Knoblach","sequence":"additional","affiliation":[{"name":"Department of Integrative Systems Biology George Washington University School of Medicine and Health Sciences  Washington DC"},{"name":"Department of Pediatrics and Center for Genetic Medicine Children's National Medical Center  Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,23]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"4","article-title":"The microglail\u2010motoneuron dialogue in ALS","volume":"30","author":"Appel S. 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