{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:43:15Z","timestamp":1793155395652,"version":"4.5.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,7,8]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Rett Syndrome is a devastating neurodevelopmental disorder that arises from mutations in the methyl-CpG binding protein 2 (\n                    <jats:italic>MeCP2<\/jats:italic>\n                    ) gene and has no presently available treatment. We show that levels of insulin-like growth factor-1 (IGF1) are reduced in male and female\n                    <jats:italic>Mecp2<\/jats:italic>\n                    mutant mice. Treating male knockout mice with recombinant human IGF1 (rhIGF1) improves a range of physiological symptoms and behaviors, increases excitatory transmission and synapse density in cortical neurons, and up-regulates molecular signals underlying these deficits. Treating symptomatic female heterozygous mice also improves a range of physiological and behavioral symptoms and normalizes maturation of cortical circuits. These findings demonstrate that rhIGF1 corrects functional, structural, and molecular mechanisms downstream of MeCP2 and may be an effective therapeutic for Rett Syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1311685111","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T04:39:14Z","timestamp":1403584754000},"page":"9941-9946","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":210,"title":["Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome"],"prefix":"10.1073","volume":"111","author":[{"given":"Jorge","family":"Castro","sequence":"first","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo I.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Showming","family":"Kwok","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Petravicz","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Woodson","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Mellios","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Tropea","sequence":"additional","affiliation":[{"name":"Neuropsychiatric Genetics Department, Trinity Center for Health Sciences, St. James Hospital, Dublin D8, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mriganka","family":"Sur","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,6,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2012.00034"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153252"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835f19a7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812394106"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138389"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610593104"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.027"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.037"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/dneu.20765","article-title":"Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease","volume":"70","author":"Yoshii A","year":"2010","unstructured":"A Yoshii, M Constantine-Paton, Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. 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