{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:56:02Z","timestamp":1781211362770,"version":"3.54.1"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011885","name":"Centre for Medical Engineering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1016\/j.nbd.2021.105316","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T19:04:54Z","timestamp":1615316694000},"page":"105316","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome"],"prefix":"10.1016","volume":"153","author":[{"given":"Prachi A.","family":"Patkee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana A.","family":"Baburamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine R.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralica","family":"Dimitrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Ciarrusta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Allsop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emer","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Kangas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grainne M.","family":"McAlonan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Rutherford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"De Vita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0005","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/(SICI)1096-9888(199704)32:4<395::AID-JMS487>3.0.CO;2-#","article-title":"Application of stable isotope tracer combined with mass spectrometric detection for studying myo-inositol uptake by cultured neurons from fetal mouse: effect of trisomy 16","volume":"32","author":"Acevedo","year":"1997","journal-title":"J. Mass Spectrom."},{"key":"10.1016\/j.nbd.2021.105316_bb0010","first-page":"184","article-title":"Glycine receptors and brain development","author":"Avila","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.nbd.2021.105316_bb0015","first-page":"1","article-title":"New approaches to studying early brain development in Down syndrome","author":"Baburamani","year":"2019","journal-title":"Dev. Med. Child Neurol."},{"key":"10.1016\/j.nbd.2021.105316_bb0020","series-title":"MRI of the Neonatal Brain","article-title":"Magnetic resonance imaging of the brain in preterm infants: 24 weeks\u2019 gestation to term","author":"Battin","year":"2002"},{"key":"10.1016\/j.nbd.2021.105316_bb0025","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1001\/archpsyc.62.12.1360","article-title":"Hippocampal myo-inositol and cognitive ability in adults with down syndrome","volume":"62","author":"Beacher","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"issue":"1","key":"10.1016\/j.nbd.2021.105316_bb0030","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S0022-3476(99)70334-3","article-title":"In vivo brain myo-inositol levels in children with Down syndrome","volume":"135","author":"Berry","year":"1999","journal-title":"J. Pediatr."},{"key":"10.1016\/j.nbd.2021.105316_bb0035","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1093\/cercor\/bhs283","article-title":"Metabolic maturation of the human brain from birth through adolescence: insights Fom in vivo magnetic resonance spectroscopy","volume":"23","author":"Bl\u00fcml","year":"2013","journal-title":"Cereb. Cortex"},{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0040","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1007\/s12640-017-9775-0","article-title":"Knockdown of myo-inositol transporter SMIT1 normalizes cholinergic and glutamatergic function in an immortalized cell line established from the cerebral cortex of a trisomy 16 fetal mouse, an animal model of human trisomy 21 (down syndrome)","volume":"32","author":"C\u00e1rdenas","year":"2017","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.nbd.2021.105316_bb0045","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s11481-013-9460-x","article-title":"Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain","author":"Chang","year":"2013","journal-title":"J. NeuroImmune Pharmacol."},{"key":"10.1016\/j.nbd.2021.105316_bb0050","first-page":"1546","article-title":"Proton MR spectroscopy in neonates with perinatal cerebral hypoxic-ischemic injury: metabolite peak-area ratios, relaxation times, and absolute concentrations","volume":"27","author":"Cheong","year":"2006","journal-title":"Am. J. Neuroradiol."},{"key":"10.1016\/j.nbd.2021.105316_bb0055","series-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988"},{"issue":"1","key":"10.1016\/j.nbd.2021.105316_bb0060","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1172\/JCI64650","article-title":"Lithium rescues synaptic plasticity and memory in Down syndrome mice","volume":"123","author":"Contestabile","year":"2013","journal-title":"J. Clin. Invest."},{"issue":"23","key":"10.1016\/j.nbd.2021.105316_bb0065","doi-asserted-by":"crossref","first-page":"E3290","DOI":"10.1073\/pnas.1606348113","article-title":"Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels","volume":"113","author":"Dai","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"2","key":"10.1016\/j.nbd.2021.105316_bb0070","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3174\/ajnr.A4512","article-title":"Elucidating metabolic maturation in the healthy fetal brain using 1H-MR spectroscopy","volume":"37","author":"Evangelou","year":"2016","journal-title":"Am. J. Neuroradiol."},{"issue":"8","key":"10.1016\/j.nbd.2021.105316_bb0075","doi-asserted-by":"crossref","first-page":"e24032","DOI":"10.1371\/journal.pone.0024032","article-title":"Sodium\/myo-inositol transporters: substrate transport requirements and regional brain expression in the TgCRND8 mouse model of amyloid pathology","volume":"6","author":"Fenili","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.nbd.2021.105316_bb0080","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1093\/brain\/awf278","article-title":"Magnetic resonance spectroscopy and cognitive function in healthy elderly men","volume":"125","author":"Ferguson","year":"2002","journal-title":"Brain"},{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0085","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1046\/j.1471-4159.2002.01041.x","article-title":"Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance","volume":"82","author":"Fisher","year":"2002","journal-title":"J. Neurochem."},{"issue":"1","key":"10.1016\/j.nbd.2021.105316_bb0090","first-page":"43","article-title":"Nonsynaptic glycine receptor activation during early neocortical development","volume":"20","author":"Flint","year":"1998","journal-title":"Neuron. Cell Press"},{"issue":"2","key":"10.1016\/j.nbd.2021.105316_bb0095","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ejrad.2005.11.021","article-title":"MRS of normal and impaired fetal brain development","volume":"57","author":"Girard","year":"2006","journal-title":"Eur. J. Radiol."},{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0100","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/nbm.1353","article-title":"Which pulse sequence is optimal for myo-inositol detection at 3T?","volume":"22","author":"Hancu","year":"2009","journal-title":"NMR Biomed."},{"key":"10.1016\/j.nbd.2021.105316_bb0105","first-page":"7","article-title":"Probing astrocyte metabolism in vivo: proton magnetic resonance spectroscopy in the injured and aging brain","author":"Harris","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.nbd.2021.105316_bb0110","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.nu.06.070186.003023","article-title":"Metabolism and function of myo-inositol and inositol phospholipids","volume":"6","author":"Holub","year":"1986","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.nbd.2021.105316_bb0115","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1176\/ajp.156.12.1879","article-title":"High brain myo-inositol levels in the predementia phase of Alzheimer\u2019s disease in adults with Down\u2019s syndrome: a 1 H MRS study","volume":"156","author":"Huang","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.nbd.2021.105316_bb0120","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/mrm.26462","article-title":"A dedicated neonatal brain imaging system","volume":"78","author":"Hughes","year":"2017","journal-title":"Magn. Reson. Med."},{"key":"10.1016\/j.nbd.2021.105316_bb0125","doi-asserted-by":"crossref","first-page":"389","DOI":"10.12688\/f1000research.7506.1","article-title":"The importance of understanding individual differences in Down syndrome","volume":"5","author":"Karmiloff-Smith","year":"2016","journal-title":"F1000Research"},{"key":"10.1016\/j.nbd.2021.105316_bb0130","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0387-7604(96)00496-2","article-title":"Neuronal maturation and N-acetyl-l-aspartic acid development in human fetal and child brains","volume":"19","author":"Kato","year":"1997","journal-title":"Brain and Development"},{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0135","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1002\/mrm.20434","article-title":"Variability of metabolite yield using STEAM or PRESS sequences in vivo at 3.0\u00a0T, illustrated with myo-inositol","volume":"53","author":"Kim","year":"2005","journal-title":"Magn. Reson. Med."},{"key":"10.1016\/j.nbd.2021.105316_bb0140","first-page":"1370","article-title":"Short echo time MR spectroscopic imaging for neonatal pediatric imaging","volume":"27","author":"Kim","year":"2006","journal-title":"Am. J. Neuroradiol."},{"issue":"5","key":"10.1016\/j.nbd.2021.105316_bb0145","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1067\/mob.2001.117677","article-title":"Metabolic information from the human fetal brain obtained with proton magnetic resonance spectroscopy","volume":"185","author":"Kok","year":"2001","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0150","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/mrm.10264","article-title":"Maturation of the human fetal brain as observed by1H MR spectroscopy","volume":"48","author":"Kok","year":"2002","journal-title":"Magn. Reson. Med."},{"key":"10.1016\/j.nbd.2021.105316_bb0155","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1474-4422(18)30325-9","article-title":"Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study","volume":"18","author":"Lally","year":"2019","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.nbd.2021.105316_bb0160","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.nicl.2016.06.001","article-title":"1H-MRS metabolites in adults with Down syndrome: effects of dementia","volume":"11","author":"Lin","year":"2016","journal-title":"NeuroImage"},{"key":"10.1016\/j.nbd.2021.105316_bb0165","series-title":"Genetically Determined Brain Abnormalities in Down Syndrome \u2013 Towards a Treatment\u202f: a Single Blind Placebo Controlled Trial of Lithium Carbonate in Down Syndrome","author":"Murphy","year":"2011"},{"issue":"3","key":"10.1016\/j.nbd.2021.105316_bb0170","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1148\/radiol.13130531","article-title":"Clinical proton MR spectroscopy in central nervous system disorders","volume":"270","author":"\u00d6z","year":"2014","journal-title":"Radiology"},{"key":"10.1016\/j.nbd.2021.105316_bb0175","doi-asserted-by":"crossref","first-page":"102139","DOI":"10.1016\/j.nicl.2019.102139","article-title":"Early alterations in cortical and cerebellar regional brain growth in down syndrome: an in vivo fetal and neonatal MRI assessment","volume":"25","author":"Patkee","year":"2020","journal-title":"NeuroImage"},{"issue":"4","key":"10.1016\/j.nbd.2021.105316_bb0180","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.neures.2007.08.007","article-title":"Mental retardation in Down syndrome: from gene dosage imbalance to molecular and cellular mechanisms","volume":"59","author":"Rachidi","year":"2007","journal-title":"Neurosci. Res."},{"issue":"2","key":"10.1016\/j.nbd.2021.105316_bb0185","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3233\/JAD-160965","article-title":"A randomized, double-blind, placebo-controlled, phase 2 study of oral ELND005 (scyllo-inositol) in young adults with down syndrome without dementia","volume":"58","author":"Rafii","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.nbd.2021.105316_bb0190","series-title":"Essentials of Behavioral Research: Methods and Data Analysis","author":"Rosenthal","year":"2008"},{"issue":"1","key":"10.1016\/j.nbd.2021.105316_bb0195","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/jon.12388","article-title":"Correcting for frequency drift in clinical brain MR spectroscopy","volume":"27","author":"Rowland","year":"2017","journal-title":"J. Neuroimaging"},{"key":"10.1016\/j.nbd.2021.105316_bb0200","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/pd.4398","article-title":"Myo-inositol in Down syndrome amniotic fluid. A case-control study","author":"Santamaria","year":"2014","journal-title":"Prenat. Diagn."},{"issue":"February","key":"10.1016\/j.nbd.2021.105316_bb0205","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1172\/JCI117696","article-title":"Polyol profiles in down syndrome","volume":"95","author":"Shetty","year":"1995","journal-title":"J. Clin. Invest."},{"issue":"6","key":"10.1016\/j.nbd.2021.105316_bb0210","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/mrm.1910330619","article-title":"Role of increased cerebral myo-inositol in the dementia of Down syndrome","volume":"33","author":"Shonk","year":"1995","journal-title":"Magn. Reson. Med."},{"issue":"1","key":"10.1016\/j.nbd.2021.105316_bb0215","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/WAD.0b013e3181875434","article-title":"Regional myo-inositol concentration in mild cognitive impairment using 1H magnetic resonance spectroscopic imaging","volume":"23","author":"Siger","year":"2009","journal-title":"Alzheimer Dis. Assoc. Disord."},{"issue":"6","key":"10.1016\/j.nbd.2021.105316_bb0220","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/S1734-1140(10)70369-8","article-title":"Amino acid metabolic processes in the temporal lobes assessed by proton magnetic resonance spectroscopy (1H MRS) in children with down syndrome","volume":"62","author":"\u015amigielska-Kuzia","year":"2010","journal-title":"Pharmacol. Rep."},{"issue":"00","key":"10.1016\/j.nbd.2021.105316_bb0225","first-page":"1","article-title":"Quantitative MRI analyses of regional brain growth in living fetuses with down syndrome","volume":"00","author":"Tarui","year":"2019","journal-title":"Cereb. Cortex"},{"issue":"11","key":"10.1016\/j.nbd.2021.105316_bb0230","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0082746","article-title":"Neonatal brain metabolite concentrations: an in vivo magnetic resonance spectroscopy study with a clinical MR system at 3\u00a0Tesla","volume":"8","author":"Tomiyasu","year":"2013","journal-title":"PLoS One"},{"issue":"6","key":"10.1016\/j.nbd.2021.105316_bb0235","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2006-3448","article-title":"Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development","volume":"120","author":"Whittle","year":"2007","journal-title":"Pediatrics"},{"issue":"1","key":"10.1016\/j.nbd.2021.105316_bb0240","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mrm.22579","article-title":"A constrained least-squares approach to the automated quantitation of in vivo 1H magnetic resonance spectroscopy data","volume":"65","author":"Wilson","year":"2011","journal-title":"Magn. Reson. Med."},{"issue":"9","key":"10.1016\/j.nbd.2021.105316_bb0245","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrn3983","article-title":"A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome","volume":"16","author":"Wiseman","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.nbd.2021.105316_bb0250","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3389\/fnmol.2018.00425","article-title":"Lithium treatment is safe in children with intellectual disability","volume":"11","author":"Yuan","year":"2018","journal-title":"Front. Mol. Neurosci."},{"issue":"8","key":"10.1016\/j.nbd.2021.105316_bb0255","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/978-1-61737-992-5_9","article-title":"MR spectroscopy and spectroscopic imaging of the brain","volume":"711","author":"Zhu","year":"2011","journal-title":"Methods Mol. Biol."}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996121000656?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996121000656?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:25:52Z","timestamp":1760851552000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996121000656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":51,"alternative-id":["S0969996121000656"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2021.105316","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.20.211805","asserted-by":"object"}]},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2021.105316","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"105316"}}