{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:57:58Z","timestamp":1777316278187,"version":"3.51.4"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007472","name":"Funda\u00e7\u00e3o Luso-Americana para o Desenvolvimento","doi-asserted-by":"publisher","award":["FLAD Life Science 2020"],"award-info":[{"award-number":["FLAD Life Science 2020"]}],"id":[{"id":"10.13039\/501100007472","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT","award":["UIDP\/04950\/2020"],"award-info":[{"award-number":["UIDP\/04950\/2020"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). This condition has been associated with an increase of gamma-aminobutyric acid (GABA) neurotransmission and, consequently, an excitation\/inhibition imbalance associated with autistic-like behavior in both human and animal models. Here, we explored the influence of biological sex in the GABAergic system and behavioral alterations induced by the <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mutation in a murine model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Juvenile male and female <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice and their wild-type (WT) littermates were used. Hippocampus size was assessed by conventional toluidine blue staining and structural magnetic resonance imaging (MRI). Hippocampal GABA and glutamate levels were determined by magnetic resonance spectroscopy (MRS), which was complemented by western blot for the GABA(A) receptor. Behavioral evaluation of on anxiety, memory, social communication, and repetitive behavior was performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that juvenile female <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice exhibited increased hippocampal GABA levels. Moreover, mutant female displays a more prominent anxious-like behavior together with better memory performance and social behavior. On the other hand, juvenile <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> male mice showed increased hippocampal volume and thickness, with a decrease in GABA(A) receptor levels. We observed that mutant males had higher tendency for repetitive behavior.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results suggested a sexually dimorphic impact of <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mutation in hippocampal neurochemistry, and autistic-like behaviors. For the first time, we identified a \u201ccamouflaging\u201d-type behavior in females of an animal model of ASD, which masked their autistic traits. Accordingly, like observed in human disorder, in this animal model of ASD, females show larger anxiety levels but better executive functions and production of normative social patterns, together with an imbalance of inhibition\/excitation ratio. Contrary, males have more externalizing disorders, such as hyperactivity and repetitive behaviors, with memory deficits. The ability of females to camouflage their autistic traits creates a phenotypic evaluation challenge that mimics the diagnosis difficulty observed in humans. Thus, we propose the study of the <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mouse model to better understand the sexual dimorphisms of ASD phenotypes and to create better diagnostic tools.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13293-023-00509-8","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T07:03:05Z","timestamp":1682492585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neurobehavioral sex-related differences in Nf1+\/\u2212 mice: female show a \u201ccamouflaging\u201d-type behavior"],"prefix":"10.1186","volume":"14","author":[{"given":"Sofia","family":"Santos","sequence":"first","affiliation":[]},{"given":"Beatriz","family":"Martins","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9","family":"Sereno","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Martins","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Castelo-Branco","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-8664","authenticated-orcid":false,"given":"Joana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"509_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/1096-8628(200022)97:2<119::AID-AJMG3>3.0.CO;2-3","volume":"97","author":"K North","year":"2000","unstructured":"North K. Neurofibromatosis type 1. J Med Genet (Semin Med Genet). 2000;97:119\u201327.","journal-title":"J Med Genet (Semin Med Genet)"},{"issue":"6","key":"509_CR2","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1007\/s10803-014-2321-5","volume":"45","author":"S Garg","year":"2015","unstructured":"Garg S, Plasschaert E, Descheemaeker MJ, Huson S, Borghgraef M, Vogels A, et al. Autism spectrum disorder profile in neurofibromatosis type I. J Autism Dev Disord. 2015;45(6):1649\u201357.","journal-title":"J Autism Dev Disord"},{"issue":"2","key":"509_CR3","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/1098-2779(2000)6:2<117::AID-MRDD5>3.0.CO;2-X","volume":"6","author":"AE Kayl","year":"2000","unstructured":"Kayl AE, Moore BD III. Behavioral phenotype of neurofibromatosis, type 1. Ment Retard Dev Disabil Res Rev. 2000;6(2):117\u201324.","journal-title":"Ment Retard Dev Disabil Res Rev"},{"issue":"6","key":"509_CR4","doi-asserted-by":"publisher","first-page":"e1642","DOI":"10.1542\/peds.2013-1868","volume":"132","author":"S Garg","year":"2013","unstructured":"Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans DG, Huson SM. Neurofibromatosis type 1 and autism spectrum disorder. Pediatrics. 2013;132(6):e1642\u20138.","journal-title":"Pediatrics"},{"issue":"21","key":"509_CR5","doi-asserted-by":"publisher","first-page":"9658","DOI":"10.1073\/pnas.88.21.9658","volume":"88","author":"DH Gutmann","year":"1991","unstructured":"Gutmann DH, Wood DL, Collins FS. Identification of the neurofibromatosis type 1 gene product. Proc Natl Acad Sci. 1991;88(21):9658\u201362.","journal-title":"Proc Natl Acad Sci"},{"issue":"132","key":"509_CR6","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/B978-0-444-62702-5.00004-4","volume":"1","author":"JL Anderson","year":"2015","unstructured":"Anderson JL, Gutmann DH. Neurofibromatosis type 1. Handb Clin Neurol. 2015;1(132):75\u201386.","journal-title":"Handb Clin Neurol"},{"issue":"10","key":"509_CR7","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1007\/s10803-016-2877-3","volume":"46","author":"DA Bilder","year":"2016","unstructured":"Bilder DA, Bakian AV, Stevenson DA, Carbone PS, Cunniff C, Goodman AB, et al. Brief report: the prevalence of neurofibromatosis type 1 among children with autism spectrum disorder identified by the autism and developmental disabilities monitoring network. J Autism Dev Disord. 2016;46(10):3369\u201376.","journal-title":"J Autism Dev Disord"},{"issue":"2","key":"509_CR8","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/ng0296-144","volume":"12","author":"G Bollag","year":"1996","unstructured":"Bollag G, Clapp DW, Shih S, Adler F, Zhang YY, Thompson P, Lange BJ, Freedman MH, McCormick F, Jacks T, Shannon K. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet. 1996;12(2):144\u20138.","journal-title":"Nat Genet"},{"issue":"1","key":"509_CR9","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1172\/JCI60578","volume":"123","author":"WJ Jessen","year":"2013","unstructured":"Jessen WJ, Miller SJ, Jousma E, Wu J, Rizvi TA, Brundage ME, Eaves D, Widemann B, Kim MO, Dombi E, Sabo J. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Investig. 2013;123(1):340\u20137.","journal-title":"J Clin Investig"},{"issue":"8","key":"509_CR10","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1177\/088307380201700813","volume":"17","author":"RM Costa","year":"2002","unstructured":"Costa RM, Silva AJ. Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. J Child Neurol. 2002;17(8):622\u20136.","journal-title":"J Child Neurol"},{"key":"509_CR11","first-page":"13","volume":"2","author":"F Mainberger","year":"2013","unstructured":"Mainberger F, Jung NH, Zenker M, Wahll\u00e4nder U, Freudenberg L, Langer S, et al. Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1. BMC Neurol. 2013;2:13.","journal-title":"BMC Neurol"},{"issue":"64","key":"509_CR12","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.cortex.2014.10.019","volume":"1","author":"MJ Ribeiro","year":"2015","unstructured":"Ribeiro MJ, Violante IR, Bernardino I, Edden RAE, Castelo-Branco M. Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1. Cortex. 2015;1(64):194\u2013208.","journal-title":"Cortex"},{"issue":"3","key":"509_CR13","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1093\/brain\/aws368","volume":"136","author":"IR Violante","year":"2013","unstructured":"Violante IR, Ribeiro MJ, Edden RA, Guimar\u00e3es P, Bernardino I, Rebola J, Cunha G, Silva E, Castelo-Branco M. GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype\u2013phenotype correlations and functional impact. Brain. 2013;136(3):918\u201325.","journal-title":"Brain"},{"issue":"9","key":"509_CR14","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1212\/WNL.0000000000003044","volume":"87","author":"IR Violante","year":"2016","unstructured":"Violante IR, Patricio M, Bernardino I, Rebola J, Abrunhosa AJ, Ferreira N, Castelo-Branco M. GABA deficiency in NF1: a multimodal [11C]-flumazenil and spectroscopy study. Neurology. 2016;87(9):897\u2013904.","journal-title":"Neurology"},{"issue":"1","key":"509_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13229-017-0166-4","volume":"8","author":"J Gon\u00e7alves","year":"2017","unstructured":"Gon\u00e7alves J, Violante IR, Sereno J, Leit\u00e3o RA, Cai Y, Abrunhosa A, et al. Testing the excitation\/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes. Mol Autism. 2017;8(1):1\u20138.","journal-title":"Mol Autism"},{"issue":"5","key":"509_CR16","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1007\/s10519-005-9040-9","volume":"36","author":"FX Coud\u00e9","year":"2006","unstructured":"Coud\u00e9 FX, Mignot C, Lyonnet S, Munnich A. Academic impairment is the most frequent complication of neurofibromatosis type-1 (NF1) in children. Behav Genet. 2006;36(5):660\u20134.","journal-title":"Behav Genet"},{"issue":"2","key":"509_CR17","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/ana.24093","volume":"75","author":"KA Diggs-Andrews","year":"2014","unstructured":"Diggs-Andrews KA, Brown JA, Gianino SM, Rubin JB, Wozniak DF, Gutmann DH. Sex is a major determinant of neuronal dysfunction in neurofibromatosis type 1. Ann Neurol. 2014;75(2):309\u201316.","journal-title":"Ann Neurol"},{"issue":"1","key":"509_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s11689-016-9159-4","volume":"8","author":"S Garg","year":"2016","unstructured":"Garg S, Heuvelman H, Huson S, Tobin H, Green J, Evans DG, et al. Sex bias in autism spectrum disorder in neurofibromatosis type 1. J Neurodev Disord. 2016;8(1):1\u20138.","journal-title":"J Neurodev Disord"},{"key":"509_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105030","volume":"144","author":"N Elmadany","year":"2020","unstructured":"Elmadany N, Logiacco F, Buonfiglioli A, Haage VC, Wright-Jin EC, Schattenberg A, Papawassiliou RM, Kettenmann H, Semtner M, Gutmann DH. Neurofibromatosis 1-mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects. Neurobiol Dis. 2020;144: 105030.","journal-title":"Neurobiol Dis"},{"issue":"7","key":"509_CR20","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1210\/en.2018-00220","volume":"159","author":"MR Bell","year":"2018","unstructured":"Bell MR. Comparing postnatal development of gonadal hormones and associated social behaviors in rats, mice, and humans. Endocrinology. 2018;159(7):2596\u2013613.","journal-title":"Endocrinology"},{"key":"509_CR21","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0297-16.2016","author":"JW VanRyzin","year":"2016","unstructured":"VanRyzin JW, Stacey JY, Perez-Pouchoulen M, McCarthy MM. Temporary depletion of microglia during the early postnatal period induces lasting sex-dependent and sex-independent effects on behavior in rats. Eneuro. 2016. https:\/\/doi.org\/10.1523\/ENEURO.0297-16.2016.","journal-title":"Eneuro"},{"issue":"19","key":"509_CR22","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.1093\/hmg\/ddx264","volume":"26","author":"HT Nguyen","year":"2017","unstructured":"Nguyen HT, Hinman MN, Guo X, Sharma A, Arakawa H, Luo G, et al. Neurofibromatosis type 1 alternative splicing is a key regulator of Ras\/ERK signaling and learning behaviors in mice. Hum Mol Genet. 2017;26(19):3797\u2013807.","journal-title":"Hum Mol Genet"},{"issue":"1","key":"509_CR23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3390\/metabo12010071","volume":"12","author":"H Ferreira","year":"2022","unstructured":"Ferreira H, Sousa AC, Sereno J, Martins J, Castelo-Branco M, Gon\u00e7alves J. Sex-dependent social and repetitive behavior and neurochemical profile in mouse model of autism spectrum disorder. Metabolites. 2022;12(1):71.","journal-title":"Metabolites"},{"issue":"10","key":"509_CR24","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.1038\/s41596-020-0382-9","volume":"15","author":"B Rein","year":"2020","unstructured":"Rein B, Ma K, Yan Z. A standardized social preference protocol for measuring social deficits in mouse models of autism. Nat Protoc. 2020;15(10):3464\u201377.","journal-title":"Nat Protoc"},{"issue":"5","key":"509_CR25","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/s41386-018-0303-6","volume":"44","author":"KR Coffey","year":"2019","unstructured":"Coffey KR, Marx RG, Neumaier JF. DeepSqueak: a deep learning-based system for detection and analysis of ultrasonic vocalizations. Neuropsychopharmacology. 2019;44(5):859\u201368.","journal-title":"Neuropsychopharmacology"},{"key":"509_CR26","doi-asserted-by":"publisher","DOI":"10.3791\/54324","author":"JM Steinbach","year":"2016","unstructured":"Steinbach JM, Garza ET, Ryan BC. Novel object exploration as a potential assay for higher order repetitive behaviors in mice. J Vis Exp. 2016. https:\/\/doi.org\/10.3791\/54324.","journal-title":"J Vis Exp"},{"key":"509_CR27","doi-asserted-by":"publisher","DOI":"10.3791\/55523","author":"CJ Miedel","year":"2017","unstructured":"Miedel CJ, Patton JM, Miedel AN, Miedel ES, Levenson JM. Assessment of spontaneous alternation, novel object recognition and limb clasping in transgenic mouse models of amyloid-\u03b2 and tau neuropathology. J Vis Exp. 2017. https:\/\/doi.org\/10.3791\/55523.","journal-title":"J Vis Exp"},{"issue":"3","key":"509_CR28","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.neuroimage.2006.01.015","volume":"31","author":"PA Yushkevich","year":"2006","unstructured":"Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S, Gee JC, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;31(3):1116\u201328.","journal-title":"Neuroimage"},{"key":"509_CR29","unstructured":"ITK-SNAP home. http:\/\/www.itksnap.org\/pmwiki\/pmwiki.php. Accessed 28 Apr 2022."},{"issue":"1","key":"509_CR30","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1111\/j.1749-6632.1987.tb32915.x","volume":"508","author":"PA Bottomley","year":"1987","unstructured":"Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci. 1987;508(1):333\u201348.","journal-title":"Ann N Y Acad Sci"},{"key":"509_CR31","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1002\/(SICI)1522-2594(199904)41:4<649::AID-MRM2>3.0.CO;2-G","volume":"41","author":"I Tk\u00e1\u010d","year":"1999","unstructured":"Tk\u00e1\u010d I, Star\u010duk Z, Choi IY, Gruetter R. In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn Reson Med. 1999;41:649\u201356.","journal-title":"Magn Reson Med"},{"issue":"4","key":"509_CR32","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/nbm.698","volume":"14","author":"SW Provencher","year":"2001","unstructured":"Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14(4):260\u20134.","journal-title":"NMR Biomed"},{"issue":"7","key":"509_CR33","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/gbb.12305","volume":"15","author":"LI Petrella","year":"2016","unstructured":"Petrella LI, Cai Y, Sereno JV, Gon\u00e7alves SI, Silva AJ, Castelo-Branco M. Brain and behaviour phenotyping of a mouse model of neurofibromatosis type-1: an MRI\/DTI study on social cognition. Genes Brain Behav. 2016;15(7):637\u201346.","journal-title":"Genes Brain Behav"},{"issue":"1","key":"509_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-020-01488-4","volume":"15","author":"F Cervi","year":"2020","unstructured":"Cervi F, Saletti V, Turner K, Peron A, Bulgheroni S, Taddei M, et al. The TAND checklist: a useful screening tool in children with tuberous sclerosis and neurofibromatosis type 1. Orphanet J Rare Dis. 2020;15(1):1\u201311.","journal-title":"Orphanet J Rare Dis"},{"issue":"4","key":"509_CR35","doi-asserted-by":"publisher","first-page":"357","DOI":"10.31887\/DCNS.2016.18.4\/jclayton","volume":"18","author":"JA Clayton","year":"2016","unstructured":"Clayton JA. Sex influences in neurological disorders: case studies and perspectives. Dialogues Clin Neurosci. 2016;18(4):357.","journal-title":"Dialogues Clin Neurosci"},{"key":"509_CR36","first-page":"195","volume":"2","author":"M Buvini\u0107","year":"2006","unstructured":"Buvini\u0107 M, Medici A, Fern\u00e1ndez E, Torres AC. Gender differentials in health. Dis Control Prior Dev Ctries. 2006;2:195\u2013210.","journal-title":"Dis Control Prior Dev Ctries"},{"issue":"4","key":"509_CR37","doi-asserted-by":"publisher","first-page":"385","DOI":"10.31887\/DCNS.2016.18.4\/rvalentino","volume":"18","author":"RJ Valentino","year":"2016","unstructured":"Valentino RJ, Bangasser DA. Sex-biased cellular signaling: molecular basis for sex differences in neuropsychiatric diseases. Dialogues Clin Neurosci. 2016;18(4):385\u201393.","journal-title":"Dialogues Clin Neurosci"},{"issue":"1","key":"509_CR38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41386-018-0111-z","volume":"44","author":"AN Kaczkurkin","year":"2019","unstructured":"Kaczkurkin AN, Raznahan A, Satterthwaite TD. Sex differences in the developing brain: insights from multimodal neuroimaging. Neuropsychopharmacology. 2019;44(1):71\u201385.","journal-title":"Neuropsychopharmacology"},{"key":"509_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104577","volume":"135","author":"S Santos","year":"2022","unstructured":"Santos S, Ferreira H, Martins J, Gon\u00e7alves J, Castelo-Branco M. Male sex bias in early and late onset neurodevelopmental disorders: shared aspects and differences in autism spectrum disorder, attention deficit\/hyperactivity disorder, and schizophrenia. Neurosci Biobehav Rev. 2022;135: 104577.","journal-title":"Neurosci Biobehav Rev"},{"issue":"12","key":"509_CR40","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1007\/s10803-009-0810-8","volume":"39","author":"SL Hartley","year":"2009","unstructured":"Hartley SL, Sikora DM. Sex differences in autism spectrum disorder: an examination of developmental functioning, autistic symptoms, and coexisting behavior problems in toddlers. J Autism Dev Disord. 2009;39(12):1715\u201322.","journal-title":"J Autism Dev Disord"},{"issue":"1","key":"509_CR41","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13229-019-0276-2","volume":"10","author":"C Harrop","year":"2019","unstructured":"Harrop C, Jones D, Zheng S, Nowell S, Schultz R, Parish-Morris J. Visual attention to faces in children with autism spectrum disorder: are there sex differences? Mol Autism. 2019;10(1):28.","journal-title":"Mol Autism"},{"issue":"5","key":"509_CR42","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1007\/s10803-013-1964-y","volume":"44","author":"T May","year":"2014","unstructured":"May T, Cornish K, Rinehart N. Does gender matter? A one year follow-up of autistic, attention and anxiety symptoms in high-functioning children with autism spectrum disorder. J Autism Dev Disord. 2014;44(5):1077\u201386.","journal-title":"J Autism Dev Disord"},{"issue":"11","key":"509_CR43","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.rasd.2014.08.004","volume":"8","author":"JL Matson","year":"2014","unstructured":"Matson JL, Adams HL. Characteristics of aggression among persons with autism spectrum disorders. Res Autism Spectr Disord. 2014;8(11):1578\u201384.","journal-title":"Res Autism Spectr Disord"},{"issue":"8","key":"509_CR44","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1007\/s10803-017-3166-5","volume":"47","author":"L Hull","year":"2017","unstructured":"Hull L, Petrides KV, Allison C, Smith P, Baron-Cohen S, Lai MC, et al. \u201cPutting on my best normal\u201d: social camouflaging in adults with autism spectrum conditions. J Autism Dev Disord. 2017;47(8):2519\u201334.","journal-title":"J Autism Dev Disord"},{"issue":"2","key":"509_CR45","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00330-006-0323-1","volume":"17","author":"PN Margariti","year":"2007","unstructured":"Margariti PN, Blekas K, Katzioti FG, Zikou AK, Tzoufi M, Argyropoulou MI. Magnetization transfer ratio and volumetric analysis of the brain in macrocephalic patients with neurofibromatosis type 1. Eur Radiol. 2007;17(2):433\u20138.","journal-title":"Eur Radiol"},{"issue":"1","key":"509_CR46","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1002\/hbm.22161","volume":"35","author":"JV Duarte","year":"2014","unstructured":"Duarte JV, Ribeiro MJ, Violante ISR, Cunha G, Silva E, Castelo-Branco M. Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1. Hum Brain Mapp. 2014;35(1):89\u2013106.","journal-title":"Hum Brain Mapp"},{"issue":"12","key":"509_CR47","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1001\/archneur.62.12.1904","volume":"62","author":"RS Greenwood","year":"2005","unstructured":"Greenwood RS, Tupler LA, Whitt JK, Buu A, Dombeck CB, Harp AG, et al. Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1. Arch Neurol. 2005;62(12):1904\u20138.","journal-title":"Arch Neurol"},{"issue":"1","key":"509_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1866-1955-5-3","volume":"5","author":"IR Violante","year":"2013","unstructured":"Violante IR, Ribeiro MJ, Silva ED, Castelo-Branco M. Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities. J Neurodev Disord. 2013;5(1):1\u201313.","journal-title":"J Neurodev Disord"},{"issue":"3","key":"509_CR49","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.cell.2008.09.060","volume":"135","author":"Y Cui","year":"2008","unstructured":"Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell. 2008;135(3):549\u201360.","journal-title":"Cell"},{"issue":"7","key":"509_CR50","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1212\/01.wnl.0000179303.72345.ce","volume":"65","author":"SL Hyman","year":"2005","unstructured":"Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology. 2005;65(7):1037\u201344.","journal-title":"Neurology"},{"issue":"1","key":"509_CR51","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.braindev.2009.12.008","volume":"33","author":"C Hachon","year":"2011","unstructured":"Hachon C, Iannuzzi S, Chaix Y. Behavioural and cognitive phenotypes in children with neurofibromatosis type 1 (NF1): the link with the neurobiological level. Brain Dev. 2011;33(1):52\u201361.","journal-title":"Brain Dev"},{"issue":"5","key":"509_CR52","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1111\/dmcn.12361","volume":"56","author":"JA Champion","year":"2014","unstructured":"Champion JA, Rose KJ, Payne JM, Burns J, North KN. Relationship between cognitive dysfunction, gait, and motor impairment in children and adolescents with neurofibromatosis type 1. Dev Med Child Neurol. 2014;56(5):468\u201374.","journal-title":"Dev Med Child Neurol"},{"issue":"10","key":"509_CR53","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1177\/0883073809358454","volume":"25","author":"NJ Ullrich","year":"2010","unstructured":"Ullrich NJ, Ayr L, Leaffer E, Irons MB, Rey-Casserly C. Pilot study of a novel computerized task to assess spatial learning in children and adolescents with neurofibromatosis type 1. J Child Neurol. 2010;25(10):1195\u2013202.","journal-title":"J Child Neurol"},{"issue":"1","key":"509_CR54","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s11689-022-09417-1","volume":"14","author":"S Mouga","year":"2022","unstructured":"Mouga S, Duarte IC, Caf\u00e9 C, Sousa D, Duque F, Oliveira G, Castelo-Branco M. Parahippocampal deactivation and hyperactivation of central executive, saliency and social cognition networks in autism spectrum disorder. J Neurodev Disord. 2022;14(1):9. https:\/\/doi.org\/10.1186\/s11689-022-09417-1.","journal-title":"J Neurodev Disord."},{"key":"509_CR55","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-022-05571-6","author":"AK Chisholm","year":"2022","unstructured":"Chisholm AK, Lami F, Haebich KM, Ure A, Brignell A, Maloof T, et al. Sex- and age-related differences in autistic behaviours in children with neurofibromatosis type 1. J Autism Dev Disord. 2022. https:\/\/doi.org\/10.1007\/s10803-022-05571-6.","journal-title":"J Autism Dev Disord"},{"issue":"8","key":"509_CR56","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1111\/j.1469-8749.2004.tb01014.x","volume":"46","author":"BA Belinda Barton","year":"2007","unstructured":"Belinda Barton BA, North K. Social skills of children with neurofibromatosis type 1. Dev Med Child Neurol. 2007;46(8):553\u201363.","journal-title":"Dev Med Child Neurol"},{"issue":"4","key":"509_CR57","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1177\/1362361310391116","volume":"15","author":"S B\u00f6lte","year":"2011","unstructured":"B\u00f6lte S, Duketis E, Poustka F, Holtmann M. Sex differences in cognitive domains and their clinical correlates in higher-functioning autism spectrum disorders. Autism. 2011;15(4):497\u2013511.","journal-title":"Autism"},{"issue":"9","key":"509_CR58","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1002\/aur.1997","volume":"11","author":"C Harrop","year":"2018","unstructured":"Harrop C, Jones D, Zheng S, Nowell SW, Boyd BA, Sasson N. Sex differences in social attention in autism spectrum disorder. Autism Res. 2018;11(9):1264\u201375.","journal-title":"Autism Res"},{"issue":"1","key":"509_CR59","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13229-015-0042-z","volume":"6","author":"K Supekar","year":"2015","unstructured":"Supekar K, Menon V. Sex differences in structural organization of motor systems and their dissociable links with repetitive\/restricted behaviors in children with autism. Mol Autism. 2015;6(1):50.","journal-title":"Mol Autism"},{"issue":"8","key":"509_CR60","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1007\/s10802-014-9881-x","volume":"42","author":"RM Hiller","year":"2014","unstructured":"Hiller RM, Young RL, Weber N. Sex differences in autism spectrum disorder based on DSM-5 criteria: evidence from clinician and teacher reporting. J Abnorm Child Psychol. 2014;42(8):1381\u201393.","journal-title":"J Abnorm Child Psychol"},{"issue":"2","key":"509_CR61","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3988\/jcn.2018.14.2.153","volume":"14","author":"R Cohen","year":"2018","unstructured":"Cohen R, Halevy A, Aharon S, Shuper A. Attention deficit hyperactivity disorder in neurofibromatosis type 1: evaluation with a continuous performance test. J Clin Neurol. 2018;14(2):153\u20137.","journal-title":"J Clin Neurol"}],"container-title":["Biology of Sex Differences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-023-00509-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13293-023-00509-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-023-00509-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T08:10:10Z","timestamp":1682496610000},"score":1,"resource":{"primary":{"URL":"https:\/\/bsd.biomedcentral.com\/articles\/10.1186\/s13293-023-00509-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["509"],"URL":"https:\/\/doi.org\/10.1186\/s13293-023-00509-8","relation":{},"ISSN":["2042-6410"],"issn-type":[{"value":"2042-6410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,26]]},"assertion":[{"value":"28 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted according to EU (2010\/63), and Portuguese (DL113\/2013) guidelines for the use of laboratory animals for scientific purposes. The project was approved by ORBEA of ICNAS, with code ORBEA 1\/2017.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24"}}