{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:43:10Z","timestamp":1793155390617,"version":"4.5.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["16\/IA\/4443"],"award-info":[{"award-number":["16\/IA\/4443"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["16\/RC\/3948"],"award-info":[{"award-number":["16\/RC\/3948"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010687","name":"H2020 Euratom","doi-asserted-by":"publisher","award":["Eit Health 19069"],"award-info":[{"award-number":["Eit Health 19069"]}],"id":[{"id":"10.13039\/100010687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001819","name":"International Rett Syndrome Foundation","doi-asserted-by":"publisher","award":["207417"],"award-info":[{"award-number":["207417"]}],"id":[{"id":"10.13039\/100001819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>MECP2<\/jats:italic>\n                    and its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett Syndrome (RTT), a rare neurodevelopmental disorder. Additional evidence suggests that\n                    <jats:italic>MECP2<\/jats:italic>\n                    may underlie other neuropsychiatric and neurological conditions, and perhaps modulate common presentations and pathophysiology across disorders. To clarify the mechanisms of these interactions, we develop a method that uses the binding properties of MeCP2 to identify its targets, and in particular, the genes recognized by MeCP2 and associated to several neurological and neuropsychiatric disorders. Analysing mechanisms and pathways modulated by these genes, we find that they are involved in three main processes: neuronal transmission, immuno-reactivity, and development. Also, while the nervous system is the most relevant in the pathophysiology of the disorders, additional systems may contribute to MeCP2 action through its target genes. We tested our results with transcriptome analysis on\n                    <jats:italic>Mecp2<\/jats:italic>\n                    -null models and cells derived from a patient with RTT, confirming that the genes identified by our procedure are directly modulated by MeCP2. Thus, MeCP2 may modulate similar mechanisms in different pathologies, suggesting that treatments for one condition may be effective for related disorders.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-79268-0","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T06:04:23Z","timestamp":1608185063000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders"],"prefix":"10.1038","volume":"10","author":[{"given":"Snow","family":"Bach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh M.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Guasoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiden P.","family":"Corvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania A.","family":"El-Nemr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyal","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Sanfeliu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Tropea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"79268_CR1","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1126\/science.1086446","volume":"302","author":"WG Chen","year":"2003","unstructured":"Chen, W. G. et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science (80-) 302, 885\u2013889 (2003).","journal-title":"Science (80-)"},{"key":"79268_CR2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s12402-017-0232-y","volume":"10","author":"S Srivastav","year":"2018","unstructured":"Srivastav, S., Walitza, S. & Gr\u00fcnblatt, E. Emerging role of miRNA in attention deficit hyperactivity disorder: a systematic review. ADHD Atten. Deficit Hyperact. Disord. 10, 49\u201363 (2018).","journal-title":"ADHD Atten. Deficit Hyperact. Disord."},{"key":"79268_CR3","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1124\/pr.111.005108","volume":"64","author":"AE Autry","year":"2012","unstructured":"Autry, A. E. & Monteggia, L. M. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol. Rev. 64, 238\u2013258 (2012).","journal-title":"Pharmacol. Rev."},{"key":"79268_CR4","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1093\/hmg\/ddi097","volume":"14","author":"K Makedonski","year":"2005","unstructured":"Makedonski, K., Abuhatzira, L., Kaufman, Y., Razin, A. & Shemer, R. MeCP2 deficiency in Rett syndrome causes epigenetic aberrations at the PWS\/AS imprinting center that affects UBE3A expression. Hum. Mol. Genet. 14, 1049\u20131058 (2005).","journal-title":"Hum. Mol. Genet."},{"key":"79268_CR5","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1086\/342931","volume":"71","author":"B Coffee","year":"2002","unstructured":"Coffee, B., Zhang, F., Ceman, S., Warren, S. T. & Reines, D. Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile X syndrome. Am. J. Hum. Genet. 71, 923\u2013932 (2002).","journal-title":"Am. J. Hum. Genet."},{"key":"79268_CR6","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1097\/MOP.0b013e32834c9251","volume":"23","author":"OS Khwaja","year":"2011","unstructured":"Khwaja, O. S. & Sahin, M. Translational research: Rett syndrome and tuberous sclerosis complex. Curr. Opin. Pediatr. 23, 633\u2013639 (2011).","journal-title":"Curr. Opin. Pediatr."},{"key":"79268_CR7","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.ijbiomac.2016.12.062","volume":"96","author":"Y Wang","year":"2017","unstructured":"Wang, Y. et al. Repression of TSC1\/TSC2 mediated by MeCP2 regulates human embryo lung fibroblast cell differentiation and proliferation. Int. J. Biol. Macromol. 96, 578\u2013588 (2017).","journal-title":"Int. J. Biol. Macromol."},{"key":"79268_CR8","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.braindev.2004.08.003","volume":"27","author":"H Li","year":"2005","unstructured":"Li, H., Yamagata, T., Mori, M., Yasuhara, A. & Momoi, M. Y. Mutation analysis of methyl-CpG binding protein family genes in autistic patients. Brain Dev. 27, 321\u2013325 (2005).","journal-title":"Brain Dev."},{"key":"79268_CR9","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s10803-013-1902-z","volume":"44","author":"B Suter","year":"2014","unstructured":"Suter, B., Treadwell-Deering, D., Zoghbi, H. Y., Glaze, D. G. & Neul, J. L. Brief report: MECP2 mutations in people without Rett syndrome. J. Autism Dev. Disord. 44, 703\u2013711 (2014).","journal-title":"J. Autism Dev. Disord."},{"key":"79268_CR10","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.molmed.2014.03.004","volume":"20","author":"J Ausi\u00f3","year":"2014","unstructured":"Ausi\u00f3, J., de Paz, A. M. & Esteller, M. MeCP2: the long trip from a chromatin protein to neurological disorders. Trends Mol. Med. 20, 487\u2013498 (2014).","journal-title":"Trends Mol. Med."},{"key":"79268_CR11","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/s41588-019-0344-8","volume":"51","author":"J Grove","year":"2019","unstructured":"Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431\u2013444 (2019).","journal-title":"Nat. Genet."},{"key":"79268_CR12","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3389\/fpsyt.2018.00251","volume":"9","author":"V Hayman","year":"2018","unstructured":"Hayman, V. & Fernandez, T. V. Genetic insights into ADHD biology. Front. Psychiatry 9, 251. https:\/\/doi.org\/10.3389\/fpsyt.2018.00251 (2018).","journal-title":"Front. Psychiatry"},{"key":"79268_CR13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","volume":"22","author":"DM Howard","year":"2019","unstructured":"Howard, D. M. et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat. Neurosci. 22, 343\u2013352 (2019).","journal-title":"Nat. Neurosci."},{"key":"79268_CR14","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s41588-019-0397-8","volume":"51","author":"EA Stahl","year":"2019","unstructured":"Stahl, E. A. et al. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat. Genet. 51, 793\u2013803 (2019).","journal-title":"Nat. Genet."},{"key":"79268_CR15","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1176\/appi.ajp.2017.16121402","volume":"174","author":"L Duncan","year":"2017","unstructured":"Duncan, L. et al. Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. Am. J. Psychiatry 174, 850\u2013858 (2017).","journal-title":"Am. J. Psychiatry"},{"key":"79268_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07524-z","author":"B Abou-Khalil","year":"2018","unstructured":"Abou-Khalil, B., Auce, P., Avbersek, A., Bahlo, M. & Balding, D. J. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat. Commun. https:\/\/doi.org\/10.1038\/s41467-018-07524-z (2018).","journal-title":"Nat. Commun."},{"key":"79268_CR17","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/ng.2802","volume":"45","author":"JC Lambert","year":"2013","unstructured":"Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease. Nat. Genet. 45, 1452\u20131458 (2013).","journal-title":"Nat. Genet."},{"key":"79268_CR18","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1038\/ng.3955","volume":"49","author":"D Chang","year":"2017","unstructured":"Chang, D. et al. A meta-analysis of genome-wide association studies identifies 17 new Parkinson\u2019s disease risk loci. Nat. Genet. 49, 1511\u20131516 (2017).","journal-title":"Nat. Genet."},{"key":"79268_CR19","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/S1474-4422(17)30161-8","volume":"16","author":"DJH Moss","year":"2017","unstructured":"Moss, D. J. H. et al. Identification of genetic variants associated with Huntington\u2019s disease progression: a genome-wide association study. Lancet Neurol. 16, 701\u2013711 (2017).","journal-title":"Lancet Neurol."},{"key":"79268_CR20","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/ng.3622","volume":"48","author":"W van Rheenen","year":"2016","unstructured":"van Rheenen, W. et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat. Genet. 48, 1043\u20131048 (2016).","journal-title":"Nat. Genet."},{"key":"79268_CR21","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1007\/s00439-015-1601-2","volume":"134","author":"VV Bashinskaya","year":"2015","unstructured":"Bashinskaya, V. V., Kulakova, O. G., Boyko, A. N., Favorov, A. V. & Favorova, O. O. A review of genome-wide association studies for multiple sclerosis: classical and hypothesis-driven approaches. Hum. Genet. 134, 1143\u20131162 (2015).","journal-title":"Hum. Genet."},{"key":"79268_CR22","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41588-018-0059-2","volume":"50","author":"AF Pardi\u00f1as","year":"2018","unstructured":"Pardi\u00f1as, A. F. et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat. Genet. 50, 381\u2013389 (2018).","journal-title":"Nat. Genet."},{"key":"79268_CR23","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.molcel.2005.07.021","volume":"19","author":"RJ Klose","year":"2005","unstructured":"Klose, R. J. et al. DNA binding selectivity of MeCP2 due to a requirement for A\/T sequences adjacent to methyl-CpG. Mol. Cell 19, 667\u2013678 (2005).","journal-title":"Mol. Cell"},{"key":"79268_CR24","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/cr.2013.110","volume":"23","author":"AK Maunakea","year":"2013","unstructured":"Maunakea, A. K., Chepelev, I., Cui, K. & Zhao, K. Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res. 23, 1256\u20131269 (2013).","journal-title":"Cell Res."},{"key":"79268_CR25","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1038\/nprot.2013.150","volume":"8","author":"S Wang","year":"2013","unstructured":"Wang, S. et al. Target analysis by integration of transcriptome and ChIP-seq data with BETA. Nat. Protoc. 8, 2502\u20132515 (2013).","journal-title":"Nat. Protoc."},{"key":"79268_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11025","author":"HT Rube","year":"2016","unstructured":"Rube, H. T. et al. Sequence features accurately predict genome-wide MeCP2 binding in vivo. Nat. Commun. https:\/\/doi.org\/10.1038\/ncomms11025 (2016).","journal-title":"Nat. Commun."},{"key":"79268_CR27","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1126\/science.1153252","volume":"320","author":"M Chahrour","year":"2008","unstructured":"Chahrour, M. et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science (80-) 320, 1224\u20131229 (2008).","journal-title":"Science (80-)"},{"key":"79268_CR28","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3389\/fpsyt.2019.00278","volume":"10","author":"A Sanfeliu","year":"2019","unstructured":"Sanfeliu, A., Hokamp, K., Gill, M. & Tropea, D. Transcriptomic analysis of Mecp2 mutant mice reveals differentially expressed genes and altered mechanisms in both blood and brain. Front. Psychiatry 10, 278 (2019).","journal-title":"Front. Psychiatry"},{"key":"79268_CR29","doi-asserted-by":"publisher","first-page":"e3669","DOI":"10.1371\/journal.pone.0003669","volume":"3","author":"RG Urdinguio","year":"2008","unstructured":"Urdinguio, R. G. et al. Mecp2-null mice provide new neuronal targets for Rett syndrome. PLoS ONE 3, e3669 (2008).","journal-title":"PLoS ONE"},{"key":"79268_CR30","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/2040-2392-4-36","volume":"4","author":"BS Abrahams","year":"2013","unstructured":"Abrahams, B. S. et al. SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). Mol. Autism 4, 36. https:\/\/doi.org\/10.1186\/2040-2392-4-36 (2013).","journal-title":"Mol. Autism"},{"key":"79268_CR31","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.ajhg.2007.09.011","volume":"82","author":"HG Kim","year":"2008","unstructured":"Kim, H. G. et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82, 199\u2013207 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"79268_CR32","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/nn.4267","volume":"19","author":"T Singh","year":"2016","unstructured":"Singh, T. et al. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nat. Neurosci. 19, 571\u2013577 (2016).","journal-title":"Nat. Neurosci."},{"key":"79268_CR33","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/mp.2011.117","volume":"17","author":"ES Lips","year":"2012","unstructured":"Lips, E. S. et al. Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia. Mol. Psychiatry 17, 996\u20131006 (2012).","journal-title":"Mol. Psychiatry"},{"key":"79268_CR34","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1471-2105-10-48","volume":"10","author":"E Eden","year":"2009","unstructured":"Eden, E., Navon, R., Steinfeld, I., Lipson, D. & Yakhini, Z. GOrilla: A tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinform. 10, 48 (2009).","journal-title":"BMC Bioinform."},{"key":"79268_CR35","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1039\/C5MB00663E","volume":"12","author":"G Yu","year":"2016","unstructured":"Yu, G. & He, Q. Y. ReactomePA: An R\/Bioconductor package for reactome pathway analysis and visualization. Mol. Biosyst. 12, 477\u2013479 (2016).","journal-title":"Mol. Biosyst."},{"key":"79268_CR36","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2307\/2340521","volume":"85","author":"RA Fisher","year":"1922","unstructured":"Fisher, R. A. On the interpretation of \u03c7 2 from contingency tables, and the calculation of P. J. R. Stat. Soc. 85, 87\u201394 (1922).","journal-title":"J. R. Stat. Soc."},{"key":"79268_CR37","doi-asserted-by":"publisher","first-page":"4179","DOI":"10.1016\/j.celrep.2020.02.107","volume":"30","author":"DC Rodrigues","year":"2020","unstructured":"Rodrigues, D. C. et al. Shifts in ribosome engagement impact key gene sets in neurodevelopment and ubiquitination in Rett syndrome. Cell Rep. 30, 4179\u20134196 (2020).","journal-title":"Cell Rep."},{"key":"79268_CR38","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1074\/mcp.M113.035600","volume":"13","author":"L Fagerberg","year":"2014","unstructured":"Fagerberg, L. et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol. Cell. Proteomics 13, 397\u2013406 (2014).","journal-title":"Mol. Cell. Proteomics"},{"key":"79268_CR39","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1250","author":"FF Operto","year":"2019","unstructured":"Operto, F. F., Mazza, R., Pastorino, G. M. G., Verrotti, A. & Coppola, G. Epilepsy and genetic in Rett syndrome: a review. Brain Behav. https:\/\/doi.org\/10.1002\/brb3.1250 (2019).","journal-title":"Brain Behav."},{"key":"79268_CR40","doi-asserted-by":"publisher","first-page":"172","DOI":"10.4161\/epi.1.4.3514","volume":"1","author":"RP Nagarajan","year":"2006","unstructured":"Nagarajan, R. P., Hogart, A. R., Gwye, Y., Martin, M. R. & LaSalle, J. M. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 1, 172\u2013182 (2006).","journal-title":"Epigenetics"},{"key":"79268_CR41","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jpsychires.2015.03.006","volume":"64","author":"Y Xu","year":"2015","unstructured":"Xu, Y. et al. Multiple epigenetic factors predict the attention deficit\/hyperactivity disorder among the Chinese Han children. J. Psychiatr. Res. 64, 40\u201350 (2015).","journal-title":"J. Psychiatr. Res."},{"key":"79268_CR42","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1002\/humu.21253","volume":"31","author":"M Zweier","year":"2010","unstructured":"Zweier, M. et al. Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. Hum. Mutat. 31, 722\u2013733 (2010).","journal-title":"Hum. Mutat."},{"key":"79268_CR43","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/npp.2012.116","volume":"38","author":"ES Na","year":"2013","unstructured":"Na, E. S., Nelson, E. D., Kavalali, E. T. & Monteggia, L. M. The impact of MeCP2 loss- or gain-of-function on synaptic plasticity. Neuropsychopharmacology 38, 212\u2013219 (2013).","journal-title":"Neuropsychopharmacology"},{"key":"79268_CR44","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/nature16533","volume":"530","author":"Z Liu","year":"2016","unstructured":"Liu, Z. et al. Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2. Nature 530, 98\u2013102 (2016).","journal-title":"Nature"},{"key":"79268_CR45","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/aur.1262","volume":"6","author":"SU Peters","year":"2013","unstructured":"Peters, S. U. et al. The behavioral phenotype in MECP2 duplication syndrome: a comparison with idiopathic autism. Autism Res. 6, 42\u201350 (2013).","journal-title":"Autism Res."},{"key":"79268_CR46","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.expneurol.2018.05.019","volume":"307","author":"DF Wong","year":"2018","unstructured":"Wong, D. F. et al. Are dopamine receptor and transporter changes in Rett syndrome reflected in Mecp2-deficient mice?. Exp. Neurol. 307, 74\u201381 (2018).","journal-title":"Exp. Neurol."},{"key":"79268_CR47","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.molmed.2011.06.009","volume":"17","author":"H Soreq","year":"2011","unstructured":"Soreq, H. & Wolf, Y. NeurimmiRs: MicroRNAs in the neuroimmune interface. Trends Mol. Med. 17, 548\u2013555 (2011).","journal-title":"Trends Mol. Med."},{"key":"79268_CR48","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1101\/gad.1519107","volume":"21","author":"J Visvanathan","year":"2007","unstructured":"Visvanathan, J., Lee, S., Lee, B., Lee, J. W. & Lee, S. K. The microRNA miR-124 antagonizes the anti-neural REST\/SCP1 pathway during embryonic CNS development. Genes Dev. 21, 744\u2013749 (2007).","journal-title":"Genes Dev."},{"key":"79268_CR49","doi-asserted-by":"publisher","first-page":"3262","DOI":"10.3390\/ijms15023262","volume":"15","author":"J Yin","year":"2014","unstructured":"Yin, J. et al. MiR-137: a new player in schizophrenia. Int. J. Mol. Sci. 15, 3262\u20133271 (2014).","journal-title":"Int. J. Mol. Sci."},{"key":"79268_CR50","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","volume":"4","author":"JW Kinney","year":"2018","unstructured":"Kinney, J. W. et al. Inflammation as a central mechanism in Alzheimer\u2019s disease. Alzheimer\u2019s Dement. Transl. Res. Clin. Interv. 4, 575\u2013590 (2018).","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"79268_CR51","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.autrev.2016.01.011","volume":"15","author":"C De Felice","year":"2016","unstructured":"De Felice, C. et al. Rett syndrome: An autoimmune disease?. Autoimmun. Rev. 15, 411\u2013416 (2016).","journal-title":"Autoimmun. Rev."},{"key":"79268_CR52","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1096\/fj.00-0399fje","volume":"15","author":"D Baker","year":"2001","unstructured":"Baker, D. et al. Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J. 15, 300\u2013302 (2001).","journal-title":"FASEB J."},{"key":"79268_CR53","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.neuropharm.2018.07.029","volume":"140","author":"D Vigli","year":"2018","unstructured":"Vigli, D. et al. Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome. Neuropharmacology 140, 121\u2013129 (2018).","journal-title":"Neuropharmacology"},{"key":"79268_CR54","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1002\/ana.410250109","volume":"25","author":"HY Zoghbi","year":"1989","unstructured":"Zoghbi, H. Y. et al. Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome. Ann. Neurol. 25, 56\u201360 (1989).","journal-title":"Ann. Neurol."},{"key":"79268_CR55","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/0887-8994(89)90049-0","volume":"5","author":"A Lekman","year":"1989","unstructured":"Lekman, A. et al. Rett syndrome: Biogenic amines and metabolites in postmortem brain. Pediatr. Neurol. 5, 357\u2013362 (1989).","journal-title":"Pediatr. Neurol."},{"key":"79268_CR56","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1136\/jnnp.53.10.915","volume":"53","author":"N Wolfe","year":"1990","unstructured":"Wolfe, N. et al. Neuropsychological profile linked to low dopamine: in Alzheimer\u2019s disease, major depression, and Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry 53, 915\u2013917 (1990).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"79268_CR57","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00052","author":"E Dobryakova","year":"2015","unstructured":"Dobryakova, E., Genova, H. M., DeLuca, J. & Wylie, G. R. The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders. Front. Neurol. https:\/\/doi.org\/10.3389\/fneur.2015.00052 (2015).","journal-title":"Front. Neurol."},{"key":"79268_CR58","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1001\/jama.2009.1308","volume":"302","author":"ND Volkow","year":"2009","unstructured":"Volkow, N. D. et al. Evaluating dopamine reward pathway in ADHD: clinical implications. J. Am. Med. Assoc. 302, 1084\u20131091 (2009).","journal-title":"J. Am. Med. Assoc."},{"key":"79268_CR59","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00260","author":"KM Money","year":"2013","unstructured":"Money, K. M. & Stanwood, G. D. Developmental origins of brain disorders: roles for dopamine. Front. Cell. Neurosci. https:\/\/doi.org\/10.3389\/fncel.2013.00260 (2013).","journal-title":"Front. Cell. Neurosci."},{"key":"79268_CR60","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S0887-8994(96)00218-4","volume":"15","author":"R Lappalainen","year":"1996","unstructured":"Lappalainen, R. & Riikonen, R. S. High levels of cerebrospinal fluid glutamate in Rett syndrome. Pediatr. Neurol. 15, 213\u2013216 (1996).","journal-title":"Pediatr. Neurol."},{"key":"79268_CR61","doi-asserted-by":"publisher","first-page":"5346","DOI":"10.1523\/JNEUROSCI.5966-09.2010","volume":"30","author":"I Maezawa","year":"2010","unstructured":"Maezawa, I. & Jin, L.-W.W. Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J. Neurosci. 30, 5346\u20135356 (2010).","journal-title":"J. Neurosci."},{"key":"79268_CR62","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.14199","author":"X Meng","year":"2016","unstructured":"Meng, X. et al. Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders. Elife https:\/\/doi.org\/10.7554\/eLife.14199 (2016).","journal-title":"Elife"},{"key":"79268_CR63","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1177\/0269881114563634","volume":"29","author":"O Howes","year":"2015","unstructured":"Howes, O., McCutcheon, R. & Stone, J. Glutamate and dopamine in schizophrenia: an update for the 21st century. J. Psychopharmacol. 29, 97\u2013115 (2015).","journal-title":"J. Psychopharmacol."},{"key":"79268_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2350-7-61","volume":"7","author":"IJ Delgado","year":"2006","unstructured":"Delgado, I. J., Kim, D. S., Thatcher, K. N., LaSalle, J. M. & Van den Veyver, I. B. Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients. BMC Med. Genet. 7, 1\u201313 (2006).","journal-title":"BMC Med. Genet."},{"key":"79268_CR65","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1080\/0264830500381435","volume":"17","author":"D Kerr","year":"2005","unstructured":"Kerr, D., Krishnan, C., Pucak, M. L. & Carmen, J. The immune system and neuropsychiatric diseases. Int. Rev. Psychiatry 17, 443\u2013449 (2005).","journal-title":"Int. Rev. Psychiatry"},{"key":"79268_CR66","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/S2215-0366(14)00122-9","volume":"2","author":"GM Khandaker","year":"2015","unstructured":"Khandaker, G. M. et al. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry 2, 258\u2013270 (2015).","journal-title":"Lancet Psychiatry"},{"key":"79268_CR67","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/S1357-4310(98)01220-9","volume":"4","author":"C Lengauer","year":"1998","unstructured":"Lengauer, C. & Issa, J.-P. The role of epigenetics in cancer. Mol. Med. Today 4, 102\u2013103 (1998).","journal-title":"Mol. Med. Today"},{"key":"79268_CR68","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10048-013-0356-y","volume":"14","author":"AR Paciorkowski","year":"2013","unstructured":"Paciorkowski, A. R. et al. MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways. Neurogenetics 14, 99\u2013111 (2013).","journal-title":"Neurogenetics"},{"key":"79268_CR69","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1126\/science.7907431","volume":"263","author":"A Ghosh","year":"1994","unstructured":"Ghosh, A., Carnahan, J. & Greenberg, M. E. Requirement for BDNF in activity-dependent survival of cortical neurons. Science (80-) 263, 1618\u20131623 (1994).","journal-title":"Science (80-)"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79268-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79268-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79268-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T20:13:30Z","timestamp":1670357610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79268-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["79268"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-79268-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/819573","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]},"assertion":[{"value":"15 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22255"}}