{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:10:18Z","timestamp":1793337018860,"version":"4.5.0"},"reference-count":161,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer\u2019s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS <jats:italic>in utero<\/jats:italic>, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3\u03b2) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model.<\/jats:p>","DOI":"10.1038\/srep45561","type":"journal-article","created":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T10:31:37Z","timestamp":1491215497000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer\u2019s-like memory deficits in the Ts65Dn mouse model of Down syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"Syed Faraz","family":"Kazim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Blanchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,3]]},"reference":[{"key":"BFsrep45561_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/B978-0-444-54299-1.00006-6","volume":"197","author":"IT Lott","year":"2012","unstructured":"Lott, I. T. Neurological phenotypes for Down syndrome across the life span. Prog Brain Res 197, 101\u2013121, doi: 10.1016\/B978-0-444-54299-1.00006-6 (2012).","journal-title":"Prog Brain Res"},{"key":"BFsrep45561_CR2","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/nrn3983","volume":"16","author":"FK Wiseman","year":"2015","unstructured":"Wiseman, F. K. et al. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nature reviews. Neuroscience 16, 564\u2013574, doi: 10.1038\/nrn3983 (2015).","journal-title":"Nature reviews. Neuroscience"},{"key":"BFsrep45561_CR3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0166-2236(02)02037-4","volume":"25","author":"O Isacson","year":"2002","unstructured":"Isacson, O., Seo, H., Lin, L., Albeck, D. & Granholm, A. C. Alzheimer\u2019s disease and Down\u2019s syndrome: roles of APP, trophic factors and ACh. Trends Neurosci 25, 79\u201384 (2002).","journal-title":"Trends Neurosci"},{"key":"BFsrep45561_CR4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0022-510X(89)90019-1","volume":"89","author":"DM Mann","year":"1989","unstructured":"Mann, D. M. & Esiri, M. M. The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down\u2019s syndrome. J Neurol Sci 89, 169\u2013179 (1989).","journal-title":"J Neurol Sci"},{"key":"BFsrep45561_CR5","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1212\/WNL.35.7.957","volume":"35","author":"KE Wisniewski","year":"1985","unstructured":"Wisniewski, K. E., Dalton, A. J., McLachlan, C., Wen, G. Y. & Wisniewski, H. M. Alzheimer\u2019s disease in Down\u2019s syndrome: clinicopathologic studies. Neurology 35, 957\u2013961 (1985).","journal-title":"Neurology"},{"key":"BFsrep45561_CR6","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/ana.410170310","volume":"17","author":"KE Wisniewski","year":"1985","unstructured":"Wisniewski, K. E., Wisniewski, H. M. & Wen, G. Y. Occurrence of neuropathological changes and dementia of Alzheimer\u2019s disease in Down\u2019s syndrome. Ann Neurol 17, 278\u2013282, doi: 10.1002\/ana.410170310 (1985).","journal-title":"Ann Neurol"},{"key":"BFsrep45561_CR7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/jir.12074","volume":"58","author":"M McCarron","year":"2014","unstructured":"McCarron, M., McCallion, P., Reilly, E. & Mulryan, N. A prospective 14-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res 58, 61\u201370, doi: 10.1111\/jir.12074 (2014).","journal-title":"J Intellect Disabil Res"},{"key":"BFsrep45561_CR8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1352\/0895-8017(2002)107<0161:IATPOA>2.0.CO;2","volume":"107","author":"WB Zigman","year":"2002","unstructured":"Zigman, W. B., Schupf, N., Urv, T., Zigman, A. & Silverman, W. Incidence and temporal patterns of adaptive behavior change in adults with mental retardation. Am J Ment Retard 107, 161\u2013174, doi: 10.1352\/0895-8017(2002)107&lt;0161:IATPOA&gt;2.0.CO;2 (2002).","journal-title":"Am J Ment Retard"},{"key":"BFsrep45561_CR9","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1159\/000330861","volume":"33","author":"AC Costa","year":"2011","unstructured":"Costa, A. C. On the promise of pharmacotherapies targeted at cognitive and neurodegenerative components of Down syndrome. Dev Neurosci 33, 414\u2013427, doi: 10.1159\/000330861 (2011).","journal-title":"Dev Neurosci"},{"key":"BFsrep45561_CR10","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/nrneurol.2012.40","volume":"8","author":"AC Costa","year":"2012","unstructured":"Costa, A. C. Alzheimer disease: Treatment of Alzheimer disease in Down syndrome. Nat Rev Neurol 8, 182\u2013184, doi: 10.1038\/nrneurol.2012.40 (2012).","journal-title":"Nat Rev Neurol"},{"key":"BFsrep45561_CR11","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.jalz.2014.10.007","volume":"11","author":"D Hartley","year":"2015","unstructured":"Hartley, D. et al. Down syndrome and Alzheimer\u2019s disease: Common pathways, common goals. Alzheimer\u2019s & dementia: the journal of the Alzheimer\u2019s Association 11, 700\u2013709, doi: 10.1016\/j.jalz.2014.10.007 (2015).","journal-title":"Alzheimer\u2019s & dementia: the journal of the Alzheimer\u2019s Association"},{"key":"BFsrep45561_CR12","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/nrd3822","volume":"11","author":"S Ness","year":"2012","unstructured":"Ness, S. et al. Down\u2019s syndrome and Alzheimer\u2019s disease: towards secondary prevention. Nat Rev Drug Discov 11, 655\u2013656, doi: 10.1038\/nrd3822 (2012).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep45561_CR13","doi-asserted-by":"publisher","first-page":"101542","DOI":"10.1155\/2012\/101542","volume":"2012","author":"N Cramer","year":"2012","unstructured":"Cramer, N. & Galdzicki, Z. From abnormal hippocampal synaptic plasticity in down syndrome mouse models to cognitive disability in down syndrome. Neural Plast 2012, 101542, doi: 10.1155\/2012\/101542 (2012).","journal-title":"Neural Plast"},{"key":"BFsrep45561_CR14","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1242\/dmm.007716","volume":"4","author":"I Das","year":"2011","unstructured":"Das, I. & Reeves, R. H. The use of mouse models to understand and improve cognitive deficits in Down syndrome. Disease models & mechanisms 4, 596\u2013606, doi: 10.1242\/dmm.007716 (2011).","journal-title":"Disease models & mechanisms"},{"key":"BFsrep45561_CR15","doi-asserted-by":"publisher","first-page":"584071","DOI":"10.1155\/2012\/584071","volume":"2012","author":"N Rueda","year":"2012","unstructured":"Rueda, N., Florez, J. & Martinez-Cue, C. Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities. Neural Plast 2012, 584071, doi: 10.1155\/2012\/584071 (2012).","journal-title":"Neural Plast"},{"key":"BFsrep45561_CR16","first-page":"263","volume":"360","author":"MT Davisson","year":"1990","unstructured":"Davisson, M. T., Schmidt, C. & Akeson, E. C. Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Progress in clinical and biological research 360, 263\u2013280 (1990).","journal-title":"Progress in clinical and biological research"},{"key":"BFsrep45561_CR17","first-page":"117","volume":"384","author":"MT Davisson","year":"1993","unstructured":"Davisson, M. T. et al. Segmental trisomy as a mouse model for Down syndrome. Progress in clinical and biological research 384, 117\u2013133 (1993).","journal-title":"Progress in clinical and biological research"},{"key":"BFsrep45561_CR18","doi-asserted-by":"crossref","first-page":"13333","DOI":"10.1073\/pnas.93.23.13333","volume":"93","author":"DM Holtzman","year":"1996","unstructured":"Holtzman, D. M. et al. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proceedings of the National Academy of Sciences of the United States of America 93, 13333\u201313338 (1996).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep45561_CR19","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/nrg1525","volume":"6","author":"D Patterson","year":"2005","unstructured":"Patterson, D. & Costa, A. C. Down syndrome and genetics - a case of linked histories. Nat Rev Genet 6, 137\u2013147, doi: 10.1038\/nrg1525 (2005).","journal-title":"Nat Rev Genet"},{"key":"BFsrep45561_CR20","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s00335-011-9321-y","volume":"22","author":"X Sturgeon","year":"2011","unstructured":"Sturgeon, X. & Gardiner, K. J. Transcript catalogs of human chromosome 21 and orthologous chimpanzee and mouse regions. Mammalian genome: official journal of the International Mammalian Genome Society 22, 261\u2013271, doi: 10.1007\/s00335-011-9321-y (2011).","journal-title":"Mammalian genome: official journal of the International Mammalian Genome Society"},{"key":"BFsrep45561_CR21","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1097\/AOG.0b013e31818c91dc","volume":"112","author":"L Toso","year":"2008","unstructured":"Toso, L. et al. Prevention of developmental delays in a Down syndrome mouse model. Obstet Gynecol 112, 1242\u20131251, doi: 10.1097\/AOG.0b013e31818c91dc (2008).","journal-title":"Obstet Gynecol"},{"key":"BFsrep45561_CR22","doi-asserted-by":"publisher","first-page":"8769","DOI":"10.1523\/jneurosci.0534-10.2010","volume":"30","author":"P Bianchi","year":"2010","unstructured":"Bianchi, P. et al. Early pharmacotherapy restores neurogenesis and cognitive performance in the Ts65Dn mouse model for Down syndrome. The Journal of neuroscience: the official journal of the Society for Neuroscience 30, 8769\u20138779, doi: 10.1523\/jneurosci.0534-10.2010 (2010).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR23","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.expneurol.2006.02.005","volume":"200","author":"S Clark","year":"2006","unstructured":"Clark, S., Schwalbe, J., Stasko, M. R., Yarowsky, P. J. & Costa, A. C. Fluoxetine rescues deficient neurogenesis in hippocampus of the Ts65Dn mouse model for Down syndrome. Experimental neurology 200, 256\u2013261, doi: 10.1016\/j.expneurol.2006.02.005 (2006).","journal-title":"Experimental neurology"},{"key":"BFsrep45561_CR24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.nbd.2013.04.016","volume":"58","author":"R Velazquez","year":"2013","unstructured":"Velazquez, R. et al. Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiology of disease 58, 92\u2013101, doi: 10.1016\/j.nbd.2013.04.016 (2013).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.neulet.2005.03.031","volume":"382","author":"AC Costa","year":"2005","unstructured":"Costa, A. C. & Grybko, M. J. Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of Down syndrome. Neuroscience letters 382, 317\u2013322, doi: 10.1016\/j.neulet.2005.03.031 (2005).","journal-title":"Neuroscience letters"},{"key":"BFsrep45561_CR26","doi-asserted-by":"publisher","first-page":"8153","DOI":"10.1523\/jneurosci.1766-04.2004","volume":"24","author":"AM Kleschevnikov","year":"2004","unstructured":"Kleschevnikov, A. M. et al. Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. The Journal of neuroscience: the official journal of the Society for Neuroscience 24, 8153\u20138160, doi: 10.1523\/jneurosci.1766-04.2004 (2004).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR27","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/S0028-3908(97)00157-3","volume":"36","author":"RJ Siarey","year":"1997","unstructured":"Siarey, R. J., Stoll, J., Rapoport, S. I. & Galdzicki, Z. Altered long-term potentiation in the young and old Ts65Dn mouse, a model for Down Syndrome. Neuropharmacology 36, 1549\u20131554 (1997).","journal-title":"Neuropharmacology"},{"key":"BFsrep45561_CR28","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3389\/fncel.2011.00029","volume":"5","author":"T Begenisic","year":"2011","unstructured":"Begenisic, T. et al. Environmental enrichment decreases GABAergic inhibition and improves cognitive abilities, synaptic plasticity, and visual functions in a mouse model of Down syndrome. Front Cell Neurosci 5, 29, doi: 10.3389\/fncel.2011.00029 (2011).","journal-title":"Front Cell Neurosci"},{"key":"BFsrep45561_CR29","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.bbr.2009.08.034","volume":"206","author":"AC Costa","year":"2010","unstructured":"Costa, A. C., Stasko, M. R., Schmidt, C. & Davisson, M. T. Behavioral validation of the Ts65Dn mouse model for Down syndrome of a genetic background free of the retinal degeneration mutation Pde6b(rd1). Behavioural brain research 206, 52\u201362, doi: 10.1016\/j.bbr.2009.08.034 (2010).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR30","doi-asserted-by":"publisher","first-page":"201ra120","DOI":"10.1126\/scitranslmed.3005983","volume":"5","author":"I Das","year":"2013","unstructured":"Das, I. et al. Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model. Sci Transl Med 5, 201ra120, doi: 10.1126\/scitranslmed.3005983 (2013).","journal-title":"Sci Transl Med"},{"key":"BFsrep45561_CR31","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0304-3940(95)12052-6","volume":"199","author":"RM Escorihuela","year":"1995","unstructured":"Escorihuela, R. M. et al. A behavioral assessment of Ts65Dn mice: a putative Down syndrome model. Neuroscience letters 199, 143\u2013146 (1995).","journal-title":"Neuroscience letters"},{"key":"BFsrep45561_CR32","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nn1860","volume":"10","author":"F Fernandez","year":"2007","unstructured":"Fernandez, F. et al. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nature neuroscience 10, 411\u2013413, doi: 10.1038\/nn1860 (2007).","journal-title":"Nature neuroscience"},{"key":"BFsrep45561_CR33","doi-asserted-by":"publisher","first-page":"467251","DOI":"10.1155\/2012\/467251","volume":"2012","author":"M Heinen","year":"2012","unstructured":"Heinen, M. et al. Adult-onset fluoxetine treatment does not improve behavioral impairments and may have adverse effects on the Ts65Dn mouse model of Down syndrome. Neural Plast 2012, 467251, doi: 10.1155\/2012\/467251 (2012).","journal-title":"Neural Plast"},{"key":"BFsrep45561_CR34","doi-asserted-by":"publisher","first-page":"e50724","DOI":"10.1371\/journal.pone.0050724","volume":"7","author":"M Incerti","year":"2012","unstructured":"Incerti, M. et al. Prenatal treatment prevents learning deficit in Down syndrome model. PloS one 7, e50724, doi: 10.1371\/journal.pone.0050724 (2012).","journal-title":"PloS one"},{"key":"BFsrep45561_CR35","doi-asserted-by":"publisher","first-page":"9217","DOI":"10.1523\/JNEUROSCI.1673-12.2012","volume":"32","author":"AM Kleschevnikov","year":"2012","unstructured":"Kleschevnikov, A. M. et al. Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists. The Journal of neuroscience: the official journal of the Society for Neuroscience 32, 9217\u20139227, doi: 10.1523\/JNEUROSCI.1673-12.2012 (2012).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbr.2004.01.012","volume":"154","author":"MR Stasko","year":"2004","unstructured":"Stasko, M. R. & Costa, A. C. Experimental parameters affecting the Morris water maze performance of a mouse model of Down syndrome. Behavioural brain research 154, 1\u201317, doi: 10.1016\/j.bbr.2004.01.012 (2004).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR37","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1515\/rns.2011.037","volume":"22","author":"R Bartesaghi","year":"2011","unstructured":"Bartesaghi, R., Guidi, S. & Ciani, E. Is it possible to improve neurodevelopmental abnormalities in Down syndrome? Rev Neurosci 22, 419\u2013455, doi: 10.1515\/rns.2011.037 (2011).","journal-title":"Rev Neurosci"},{"key":"BFsrep45561_CR38","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1159\/000354306","volume":"141","author":"J Busciglio","year":"2013","unstructured":"Busciglio, J., Capone, G., O\u2019Bryan, J. & Gardiner, K. J. Down syndrome: genes, model systems, and progress towards pharmacotherapies and clinical trials for cognitive deficits. Cytogenetic and genome research 141, 260\u2013271, doi: 10.1159\/000354306 (2013).","journal-title":"Cytogenetic and genome research"},{"key":"BFsrep45561_CR39","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.autrev.2012.10.013","volume":"12","author":"ME Weksler","year":"2013","unstructured":"Weksler, M. E. et al. Alzheimer\u2019s disease and Down\u2019s syndrome: treating two paths to dementia. Autoimmunity reviews 12, 670\u2013673, doi: 10.1016\/j.autrev.2012.10.013 (2013).","journal-title":"Autoimmunity reviews"},{"key":"BFsrep45561_CR40","doi-asserted-by":"publisher","first-page":"13843","DOI":"10.1523\/jneurosci.2775-15.2015","volume":"35","author":"R Bartesaghi","year":"2015","unstructured":"Bartesaghi, R. et al. New Perspectives for the Rescue of Cognitive Disability in Down Syndrome. The Journal of neuroscience: the official journal of the Society for Neuroscience 35, 13843\u201313852, doi: 10.1523\/jneurosci.2775-15.2015 (2015).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR41","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/gco.0000000000000056","volume":"26","author":"F Guedj","year":"2014","unstructured":"Guedj, F., Bianchi, D. W. & Delabar, J. M. Prenatal treatment of Down syndrome: a reality? Current opinion in obstetrics & gynecology 26, 92\u2013103, doi: 10.1097\/gco.0000000000000056 (2014).","journal-title":"Current opinion in obstetrics & gynecology"},{"key":"BFsrep45561_CR42","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3389\/fnbeh.2015.00265","volume":"9","author":"F Stagni","year":"2015","unstructured":"Stagni, F., Giacomini, A., Guidi, S., Ciani, E. & Bartesaghi, R. Timing of therapies for Down syndrome: the sooner, the better. Frontiers in behavioral neuroscience 9, 265, doi: 10.3389\/fnbeh.2015.00265 (2015).","journal-title":"Frontiers in behavioral neuroscience"},{"key":"BFsrep45561_CR43","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.tins.2011.11.001","volume":"35","author":"TF Haydar","year":"2012","unstructured":"Haydar, T. F. & Reeves, R. H. Trisomy 21 and early brain development. Trends Neurosci 35, 81\u201391, doi: 10.1016\/j.tins.2011.11.001 (2012).","journal-title":"Trends Neurosci"},{"key":"BFsrep45561_CR44","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/nm0116-6","volume":"22","author":"BM Kuehn","year":"2016","unstructured":"Kuehn, B. M. Treating trisomies: Prenatal Down\u2019s syndrome therapies explored in mice. Nature medicine 22, 6\u20137, doi: 10.1038\/nm0116-6 (2016).","journal-title":"Nature medicine"},{"key":"BFsrep45561_CR45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0149-7634(03)00005-8","volume":"27","author":"SL Andersen","year":"2003","unstructured":"Andersen, S. L. Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27, 3\u201318 (2003).","journal-title":"Neurosci Biobehav Rev"},{"key":"BFsrep45561_CR46","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3727\/105221608786883799","volume":"14","author":"P Bernd","year":"2008","unstructured":"Bernd, P. The role of neurotrophins during early development. Gene expression 14, 241\u2013250 (2008).","journal-title":"Gene expression"},{"key":"BFsrep45561_CR47","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s11689-009-9027-6","volume":"1","author":"CA Chapleau","year":"2009","unstructured":"Chapleau, C. A., Larimore, J. L., Theibert, A. & Pozzo-Miller, L. Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism. Journal of neurodevelopmental disorders 1, 185\u2013196, doi: 10.1007\/s11689-009-9027-6 (2009).","journal-title":"Journal of neurodevelopmental disorders"},{"key":"BFsrep45561_CR48","first-page":"246","volume":"161","author":"DM Holtzman","year":"1994","unstructured":"Holtzman, D. M. & Mobley, W. C. Neurotrophic factors and neurologic disease. The Western journal of medicine 161, 246\u2013254 (1994).","journal-title":"The Western journal of medicine"},{"key":"BFsrep45561_CR49","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/s0166-2236(02)00038-3","volume":"26","author":"A Salehi","year":"2003","unstructured":"Salehi, A., Delcroix, J. D. & Mobley, W. C. Traffic at the intersection of neurotrophic factor signaling and neurodegeneration. Trends Neurosci 26, 73\u201380, doi: 10.1016\/s0166-2236(02)00038-3 (2003).","journal-title":"Trends Neurosci"},{"key":"BFsrep45561_CR50","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.neuron.2006.05.022","volume":"51","author":"A Salehi","year":"2006","unstructured":"Salehi, A. et al. Increased App expression in a mouse model of Down\u2019s syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51, 29\u201342, doi: 10.1016\/j.neuron.2006.05.022 (2006).","journal-title":"Neuron"},{"key":"BFsrep45561_CR51","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/978-1-4614-0653-2_22","volume":"724","author":"G Pagano","year":"2012","unstructured":"Pagano, G. & Castello, G. Oxidative stress and mitochondrial dysfunction in Down syndrome. Advances in experimental medicine and biology 724, 291\u2013299, doi: 10.1007\/978-1-4614-0653-2_22 (2012).","journal-title":"Advances in experimental medicine and biology"},{"key":"BFsrep45561_CR52","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1111\/j.1471-4159.2004.02990.x","volume":"92","author":"N Kaur","year":"2005","unstructured":"Kaur, N., Lu, B., Monroe, R. K., Ward, S. M. & Halvorsen, S. W. Inducers of oxidative stress block ciliary neurotrophic factor activation of Jak\/STAT signaling in neurons. Journal of neurochemistry 92, 1521\u20131530, doi: 10.1111\/j.1471-4159.2004.02990.x (2005).","journal-title":"Journal of neurochemistry"},{"key":"BFsrep45561_CR53","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/nm0602-620","volume":"8","author":"RA Linker","year":"2002","unstructured":"Linker, R. A. et al. CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nature medicine 8, 620\u2013624, doi: 10.1038\/nm0602-620 (2002).","journal-title":"Nature medicine"},{"key":"BFsrep45561_CR54","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.cytogfr.2015.07.007","volume":"26","author":"S Pasquin","year":"2015","unstructured":"Pasquin, S., Sharma, M. & Gauchat, J. F. Ciliary neurotrophic factor (CNTF): New facets of an old molecule for treating neurodegenerative and metabolic syndrome pathologies. Cytokine Growth Factor Rev 26, 507\u2013515, doi: 10.1016\/j.cytogfr.2015.07.007 (2015).","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFsrep45561_CR55","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s12035-012-8284-7","volume":"46","author":"A Tlili","year":"2012","unstructured":"Tlili, A. et al. BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients. Molecular neurobiology 46, 297\u2013303, doi: 10.1007\/s12035-012-8284-7 (2012).","journal-title":"Molecular neurobiology"},{"key":"BFsrep45561_CR56","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nrn3505","volume":"14","author":"B Lu","year":"2013","unstructured":"Lu, B., Nagappan, G., Guan, X., Nathan, P. J. & Wren, P. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nature reviews. Neuroscience 14, 401\u2013416, doi: 10.1038\/nrn3505 (2013).","journal-title":"Nature reviews. Neuroscience"},{"key":"BFsrep45561_CR57","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nm.1912","volume":"15","author":"AH Nagahara","year":"2009","unstructured":"Nagahara, A. H. et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer\u2019s disease. Nature medicine 15, 331\u2013337, doi: 10.1038\/nm.1912 (2009).","journal-title":"Nature medicine"},{"key":"BFsrep45561_CR58","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0165-0173(99)00013-2","volume":"30","author":"I Semkova","year":"1999","unstructured":"Semkova, I. & Krieglstein, J. Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain research. Brain research reviews 30, 176\u2013188 (1999).","journal-title":"Brain research. Brain research reviews"},{"key":"BFsrep45561_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2047-9158-1-14","volume":"1","author":"AM Weissmiller","year":"2012","unstructured":"Weissmiller, A. M. & Wu, C. Current advances in using neurotrophic factors to treat neurodegenerative disorders. Translational neurodegeneration 1, 1\u20139, doi: 10.1186\/2047-9158-1-14 (2012).","journal-title":"Translational neurodegeneration"},{"key":"BFsrep45561_CR60","doi-asserted-by":"crossref","unstructured":"ACTSG. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 46, 1244\u20131249 (1996).","DOI":"10.1212\/WNL.46.5.1244"},{"key":"BFsrep45561_CR61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2174\/1389203013381125","volume":"2","author":"ZY Chen","year":"2001","unstructured":"Chen, Z. Y. et al. Development of neurotrophic molecules for treatment of neurodegeneration. Curr Protein Pept Sci 2, 261\u2013276 (2001).","journal-title":"Curr Protein Pept Sci"},{"key":"BFsrep45561_CR62","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/14660820050515197","volume":"1","author":"G Ochs","year":"2000","unstructured":"Ochs, G. et al. A phase I\/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1, 201\u2013206 (2000).","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"key":"BFsrep45561_CR63","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13024-016-0119-y","volume":"11","author":"SF Kazim","year":"2016","unstructured":"Kazim, S. F. & Iqbal, K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer\u2019s disease. Molecular neurodegeneration 11, 50, doi: 10.1186\/s13024-016-0119-y (2016).","journal-title":"Molecular neurodegeneration"},{"key":"BFsrep45561_CR64","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.3233\/JAD-2004-6S606","volume":"6","author":"FM Longo","year":"2004","unstructured":"Longo, F. M. & Massa, S. M. Neurotrophin-based strategies for neuroprotection. Journal of Alzheimer\u2019s disease: JAD 6, S13\u201317 (2004).","journal-title":"Journal of Alzheimer\u2019s disease: JAD"},{"key":"BFsrep45561_CR65","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrd4024","volume":"12","author":"FM Longo","year":"2013","unstructured":"Longo, F. M. & Massa, S. M. Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease. Nat Rev Drug Discov 12, 507\u2013525 (2013).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep45561_CR66","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1016\/j.neurobiolaging.2014.02.017","volume":"35","author":"S Bolognin","year":"2014","unstructured":"Bolognin, S., Buffelli, M., Puolivali, J. & Iqbal, K. Rescue of cognitive-aging by administration of a neurogenic and\/or neurotrophic compound. Neurobiology of aging 35, 2134\u20132146, doi: 10.1016\/j.neurobiolaging.2014.02.017 (2014).","journal-title":"Neurobiology of aging"},{"key":"BFsrep45561_CR67","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.nbd.2014.07.001","volume":"71","author":"SF Kazim","year":"2014","unstructured":"Kazim, S. F. et al. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer\u2019s disease. Neurobiology of disease 71, 110\u2013130, doi: 10.1016\/j.nbd.2014.07.001 (2014).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR68","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3233\/JAD-142799","volume":"47","author":"S Khatoon","year":"2015","unstructured":"Khatoon, S., Chalbot, S., Bolognin, S., Puolivali, J. & Iqbal, K. Elevated Tau Level in Aged Rat Cerebrospinal Fluid Reduced by Treatment with a Neurotrophic Compound. Journal of Alzheimer\u2019s disease: JAD 47, 557\u2013564, doi: 10.3233\/JAD-142799 (2015).","journal-title":"Journal of Alzheimer\u2019s disease: JAD"},{"key":"BFsrep45561_CR69","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1016\/j.febslet.2010.06.025","volume":"584","author":"B Li","year":"2010","unstructured":"Li, B. et al. Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett 584, 3359\u20133365, doi: 10.1016\/j.febslet.2010.06.025 (2010).","journal-title":"FEBS Lett"},{"key":"BFsrep45561_CR70","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1097\/NEN.0b013e318236e9ad","volume":"70","author":"J Blanchard","year":"2011","unstructured":"Blanchard, J. et al. Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome. J Neuropathol Exp Neurol 70, 1070\u20131079, doi: 10.1097\/NEN.0b013e318236e9ad (2011).","journal-title":"J Neuropathol Exp Neurol"},{"key":"BFsrep45561_CR71","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3233\/JAD-2010-1000069","volume":"21","author":"J Blanchard","year":"2010","unstructured":"Blanchard, J. et al. Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice. Journal of Alzheimer\u2019s disease: JAD 21, 1185\u20131195, doi: 10.3233\/JAD-2010-1000069 (2010).","journal-title":"Journal of Alzheimer\u2019s disease: JAD"},{"key":"BFsrep45561_CR72","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s00401-010-0734-6","volume":"120","author":"J Blanchard","year":"2010","unstructured":"Blanchard, J. et al. Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Abeta and tau pathologies in 3xTg-AD mice. Acta neuropathologica 120, 605\u2013621, doi: 10.1007\/s00401-010-0734-6 (2010).","journal-title":"Acta neuropathologica"},{"key":"BFsrep45561_CR73","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s00401-011-0908-x","volume":"123","author":"S Bolognin","year":"2012","unstructured":"Bolognin, S. et al. An experimental rat model of sporadic Alzheimer\u2019s disease and rescue of cognitive impairment with a neurotrophic peptide. Acta neuropathologica 123, 133\u2013151, doi: 10.1007\/s00401-011-0908-x (2012).","journal-title":"Acta neuropathologica"},{"key":"BFsrep45561_CR74","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1227\/NEU.0000000000000577","volume":"76","author":"MO Chohan","year":"2015","unstructured":"Chohan, M. O. et al. Enhancement of neurogenesis and memory by a neurotrophic peptide in mild to moderate traumatic brain injury. Neurosurgery 76, 201\u2013214 discussion 214\u2013205, doi: 10.1227\/NEU.0000000000000577 (2015).","journal-title":"Neurosurgery"},{"key":"BFsrep45561_CR75","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.neurobiolaging.2009.08.008","volume":"32","author":"MO Chohan","year":"2011","unstructured":"Chohan, M. O. et al. Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiology of aging 32, 1420\u20131434, doi: 10.1016\/j.neurobiolaging.2009.08.008 (2011).","journal-title":"Neurobiology of aging"},{"key":"BFsrep45561_CR76","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/ng1095-177","volume":"11","author":"RH Reeves","year":"1995","unstructured":"Reeves, R. H. et al. A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet 11, 177\u2013184, doi: 10.1038\/ng1095-177 (1995).","journal-title":"Nat Genet"},{"key":"BFsrep45561_CR77","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.2144\/03356st02","volume":"35","author":"DP Liu","year":"2003","unstructured":"Liu, D. P., Schmidt, C., Billings, T. & Davisson, M. T. Quantitative PCR genotyping assay for the Ts65Dn mouse model of Down syndrome. Biotechniques 35, 1170\u20131174, 1176, 1178 passim (2003).","journal-title":"Biotechniques"},{"key":"BFsrep45561_CR78","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0149-7634(03)00016-2","volume":"27","author":"I Branchi","year":"2003","unstructured":"Branchi, I., Bichler, Z., Berger-Sweeney, J. & Ricceri, L. Animal models of mental retardation: from gene to cognitive function. Neurosci Biobehav Rev 27, 141\u2013153 (2003).","journal-title":"Neurosci Biobehav Rev"},{"key":"BFsrep45561_CR79","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-1-60327-099-1_10","volume":"39","author":"JM Hill","year":"2007","unstructured":"Hill, J. M., Lim, M. A. & Stone, M. M. Developmental Milestones in the Newborn Mouse. Neuromethods, Neuropeptide Techniques 39, 131\u2013149 (2007).","journal-title":"Neuromethods, Neuropeptide Techniques"},{"key":"BFsrep45561_CR80","doi-asserted-by":"publisher","first-page":"e0118627","DOI":"10.1371\/journal.pone.0118627","volume":"10","author":"SF Kazim","year":"2015","unstructured":"Kazim, S. F. et al. Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats. PloS one 10, e0118627, doi: 10.1371\/journal.pone.0118627 (2015).","journal-title":"PloS one"},{"key":"BFsrep45561_CR81","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.bbr.2004.06.019","volume":"157","author":"A Lubics","year":"2005","unstructured":"Lubics, A. et al. Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury. Behavioural brain research 157, 157\u2013165, doi: 10.1016\/j.bbr.2004.06.019 (2005).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR82","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0165-0270(85)90031-7","volume":"14","author":"S Pellow","year":"1985","unstructured":"Pellow, S., Chopin, P., File, S. E. & Briley, M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14, 149\u2013167 (1985).","journal-title":"J Neurosci Methods"},{"key":"BFsrep45561_CR83","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.bbr.2012.03.022","volume":"232","author":"S Akkerman","year":"2012","unstructured":"Akkerman, S. et al. Object recognition testing: methodological considerations on exploration and discrimination measures. Behavioural brain research 232, 335\u2013347, doi: 10.1016\/j.bbr.2012.03.022 (2012).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR84","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.bbr.2009.12.036","volume":"215","author":"A Ennaceur","year":"2010","unstructured":"Ennaceur, A. One-trial object recognition in rats and mice: methodological and theoretical issues. Behavioural brain research 215, 244\u2013254, doi: 10.1016\/j.bbr.2009.12.036 (2010).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR85","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0166-4328(02)00238-3","volume":"138","author":"F Sargolini","year":"2003","unstructured":"Sargolini, F., Roullet, P., Oliverio, A. & Mele, A. Effects of intra-accumbens focal administrations of glutamate antagonists on object recognition memory in mice. Behavioural brain research 138, 153\u2013163 (2003).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR86","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/297681a0","volume":"297","author":"RG Morris","year":"1982","unstructured":"Morris, R. G., Garrud, P., Rawlins, J. N. & O\u2019Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297, 681\u2013683 (1982).","journal-title":"Nature"},{"key":"BFsrep45561_CR87","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s12035-012-8375-5","volume":"47","author":"Y Chen","year":"2013","unstructured":"Chen, Y. et al. A non-transgenic mouse model (icv-STZ mouse) of Alzheimer\u2019s disease: similarities to and differences from the transgenic model (3xTg-AD mouse). Molecular neurobiology 47, 711\u2013725, doi: 10.1007\/s12035-012-8375-5 (2013).","journal-title":"Molecular neurobiology"},{"key":"BFsrep45561_CR88","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0003-2697(76)80064-4","volume":"70","author":"A Bensadoun","year":"1976","unstructured":"Bensadoun, A. & Weinstein, D. Assay of proteins in the presence of interfering materials. Analytical biochemistry 70, 241\u2013250 (1976).","journal-title":"Analytical biochemistry"},{"key":"BFsrep45561_CR89","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0031-3955(16)38548-0","volume":"40","author":"A Hayes","year":"1993","unstructured":"Hayes, A. & Batshaw, M. L. Down syndrome. Pediatr Clin North Am 40, 523\u2013535 (1993).","journal-title":"Pediatr Clin North Am"},{"key":"BFsrep45561_CR90","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1038\/labinvest.2012.117","volume":"92","author":"C Fuchs","year":"2012","unstructured":"Fuchs, C., Ciani, E., Guidi, S., Trazzi, S. & Bartesaghi, R. Early-occurring proliferation defects in peripheral tissues of the Ts65Dn mouse model of Down syndrome are associated with patched1 over expression. Lab Invest 92, 1648\u20131660, doi: 10.1038\/labinvest.2012.117 (2012).","journal-title":"Lab Invest"},{"key":"BFsrep45561_CR91","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1002\/ana.410200413","volume":"20","author":"LE Becker","year":"1986","unstructured":"Becker, L. E., Armstrong, D. L. & Chan, F. Dendritic atrophy in children with Down\u2019s syndrome. Ann Neurol 20, 520\u2013526, doi: 10.1002\/ana.410200413 (1986).","journal-title":"Ann Neurol"},{"key":"BFsrep45561_CR92","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1365-2990.2007.00899.x","volume":"34","author":"EC Downes","year":"2008","unstructured":"Downes, E. C. et al. Loss of synaptophysin and synaptosomal-associated protein 25-kDa (SNAP-25) in elderly Down syndrome individuals. Neuropathology and applied neurobiology 34, 12\u201322, doi: 10.1111\/j.1365-2990.2007.00899.x (2008).","journal-title":"Neuropathology and applied neurobiology"},{"key":"BFsrep45561_CR93","doi-asserted-by":"crossref","unstructured":"Weitzdoerfer, R., Dierssen, M., Fountoulakis, M. & Lubec, G. Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. Journal of neural transmission. Supplementum, 59\u201370 (2001).","DOI":"10.1007\/978-3-7091-6262-0_5"},{"key":"BFsrep45561_CR94","first-page":"274","volume":"7","author":"KE Wisniewski","year":"1990","unstructured":"Wisniewski, K. E. Down syndrome children often have brain with maturation delay, retardation of growth, and cortical dysgenesis. American journal of medical genetics. Supplement 7, 274\u2013281 (1990).","journal-title":"American journal of medical genetics. Supplement"},{"key":"BFsrep45561_CR95","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S0092-8674(85)80082-9","volume":"41","author":"B Wiedenmann","year":"1985","unstructured":"Wiedenmann, B. & Franke, W. W. Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell 41, 1017\u20131028 (1985).","journal-title":"Cell"},{"key":"BFsrep45561_CR96","doi-asserted-by":"publisher","first-page":"11483","DOI":"10.1523\/jneurosci.3406-07.2007","volume":"27","author":"L Chakrabarti","year":"2007","unstructured":"Chakrabarti, L., Galdzicki, Z. & Haydar, T. F. Defects in embryonic neurogenesis and initial synapse formation in the forebrain of the Ts65Dn mouse model of Down syndrome. The Journal of neuroscience: the official journal of the Society for Neuroscience 27, 11483\u201311495, doi: 10.1523\/jneurosci.3406-07.2007 (2007).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR97","doi-asserted-by":"publisher","first-page":"6329","DOI":"10.1523\/jneurosci.5968-10.2011","volume":"31","author":"X Chen","year":"2011","unstructured":"Chen, X. et al. PSD-95 is required to sustain the molecular organization of the postsynaptic density. The Journal of neuroscience: the official journal of the Society for Neuroscience 31, 6329\u20136338, doi: 10.1523\/jneurosci.5968-10.2011 (2011).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR98","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1146\/annurev.biochem.74.082803.133339","volume":"74","author":"L Funke","year":"2005","unstructured":"Funke, L., Dakoji, S. & Bredt, D. S. Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annual review of biochemistry 74, 219\u2013245, doi: 10.1146\/annurev.biochem.74.082803.133339 (2005).","journal-title":"Annual review of biochemistry"},{"key":"BFsrep45561_CR99","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nn.2505","volume":"13","author":"Y Ji","year":"2010","unstructured":"Ji, Y. et al. Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons. Nature neuroscience 13, 302\u2013309, doi: 10.1038\/nn.2505 (2010).","journal-title":"Nature neuroscience"},{"key":"BFsrep45561_CR100","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1126\/science.7886457","volume":"267","author":"H Kang","year":"1995","unstructured":"Kang, H. & Schuman, E. M. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267, 1658\u20131662 (1995).","journal-title":"Science"},{"key":"BFsrep45561_CR101","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0028-3908(98)00035-5","volume":"37","author":"M Korte","year":"1998","unstructured":"Korte, M., Kang, H., Bonhoeffer, T. & Schuman, E. A role for BDNF in the late-phase of hippocampal long-term potentiation. Neuropharmacology 37, 553\u2013559 (1998).","journal-title":"Neuropharmacology"},{"key":"BFsrep45561_CR102","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.nlm.2007.08.018","volume":"89","author":"Y Lu","year":"2008","unstructured":"Lu, Y., Christian, K. & Lu, B. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 89, 312\u2013323, doi: 10.1016\/j.nlm.2007.08.018 (2008).","journal-title":"Neurobiol Learn Mem"},{"key":"BFsrep45561_CR103","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1046\/j.1471-4159.2002.01085.x","volume":"82","author":"J Lee","year":"2002","unstructured":"Lee, J., Duan, W. & Mattson, M. P. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. Journal of neurochemistry 82, 1367\u20131375 (2002).","journal-title":"Journal of neurochemistry"},{"key":"BFsrep45561_CR104","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3389\/fnins.2016.00026","volume":"10","author":"M Vilar","year":"2016","unstructured":"Vilar, M. & Mira, H. Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles. Frontiers in neuroscience 10, 26, doi: 10.3389\/fnins.2016.00026 (2016).","journal-title":"Frontiers in neuroscience"},{"key":"BFsrep45561_CR105","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/378785a0","volume":"378","author":"DA Cross","year":"1995","unstructured":"Cross, D. A., Alessi, D. R., Cohen, P., Andjelkovich, M. & Hemmings, B. A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378, 785\u2013789, doi: 10.1038\/378785a0 (1995).","journal-title":"Nature"},{"key":"BFsrep45561_CR106","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.nbd.2014.03.003","volume":"67","author":"S Trazzi","year":"2014","unstructured":"Trazzi, S. et al. APP-dependent alteration of GSK3beta activity impairs neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiology of disease 67, 24\u201336, doi: 10.1016\/j.nbd.2014.03.003 (2014).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR107","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/j.1750-3639.2008.00246.x","volume":"20","author":"P Bianchi","year":"2010","unstructured":"Bianchi, P., Ciani, E., Contestabile, A., Guidi, S. & Bartesaghi, R. Lithium restores neurogenesis in the subventricular zone of the Ts65Dn mouse, a model for Down syndrome. Brain pathology (Zurich, Switzerland) 20, 106\u2013118, doi: 10.1111\/j.1750-3639.2008.00246.x (2010).","journal-title":"Brain pathology (Zurich, Switzerland)"},{"key":"BFsrep45561_CR108","doi-asserted-by":"crossref","first-page":"13445","DOI":"10.1073\/pnas.93.24.13445","volume":"93","author":"CH Bailey","year":"1996","unstructured":"Bailey, C. H., Bartsch, D. & Kandel, E. R. Toward a molecular definition of long-term memory storage. Proceedings of the National Academy of Sciences of the United States of America 93, 13445\u201313452 (1996).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep45561_CR109","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s10519-006-9051-1","volume":"36","author":"K Gardiner","year":"2006","unstructured":"Gardiner, K. Transcriptional dysregulation in Down syndrome: predictions for altered protein complex stoichiometries and post-translational modifications, and consequences for learning\/behavior genes ELK, CREB, and the estrogen and glucocorticoid receptors. Behav Genet 36, 439\u2013453, doi: 10.1007\/s10519-006-9051-1 (2006).","journal-title":"Behav Genet"},{"key":"BFsrep45561_CR110","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.nbd.2012.11.017","volume":"52","author":"X Altafaj","year":"2013","unstructured":"Altafaj, X. et al. Normalization of Dyrk1A expression by AAV2\/1-shDyrk1A attenuates hippocampal-dependent defects in the Ts65Dn mouse model of Down syndrome. Neurobiology of disease 52, 117\u2013127, doi: 10.1016\/j.nbd.2012.11.017 (2013).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR111","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.mcn.2010.06.013","volume":"45","author":"Y Fukuda","year":"2010","unstructured":"Fukuda, Y. et al. Stimulated neuronal expression of brain-derived neurotrophic factor by Neurotropin. Molecular and cellular neurosciences 45, 226\u2013233, doi: 10.1016\/j.mcn.2010.06.013 (2010).","journal-title":"Molecular and cellular neurosciences"},{"key":"BFsrep45561_CR112","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/364821a0","volume":"364","author":"P Brindle","year":"1993","unstructured":"Brindle, P., Linke, S. & Montminy, M. Protein-kinase-A-dependent activator in transcription factor CREB reveals new role for CREM repressors. Nature 364, 821\u2013824, doi: 10.1038\/364821a0 (1993).","journal-title":"Nature"},{"key":"BFsrep45561_CR113","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/0092-8674(89)90013-5","volume":"59","author":"GA Gonzalez","year":"1989","unstructured":"Gonzalez, G. A. & Montminy, M. R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59, 675\u2013680 (1989).","journal-title":"Cell"},{"key":"BFsrep45561_CR114","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/nrm3432","volume":"13","author":"SS Taylor","year":"2012","unstructured":"Taylor, S. S., Ilouz, R., Zhang, P. & Kornev, A. P. Assembly of allosteric macromolecular switches: lessons from PKA. Nature reviews. Molecular cell biology 13, 646\u2013658, doi: 10.1038\/nrm3432 (2012).","journal-title":"Nature reviews. Molecular cell biology"},{"key":"BFsrep45561_CR115","doi-asserted-by":"publisher","first-page":"14515","DOI":"10.1073\/pnas.0406344101","volume":"101","author":"NJ Broadbent","year":"2004","unstructured":"Broadbent, N. J., Squire, L. R. & Clark, R. E. Spatial memory, recognition memory, and the hippocampus. Proceedings of the National Academy of Sciences of the United States of America 101, 14515\u201314520, doi: 10.1073\/pnas.0406344101 (2004).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep45561_CR116","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1146\/annurev.neuro.27.070203.144130","volume":"27","author":"LR Squire","year":"2004","unstructured":"Squire, L. R., Stark, C. E. & Clark, R. E. The medial temporal lobe. Annu Rev Neurosci 27, 279\u2013306, doi: 10.1146\/annurev.neuro.27.070203.144130 (2004).","journal-title":"Annu Rev Neurosci"},{"key":"BFsrep45561_CR117","doi-asserted-by":"publisher","first-page":"681","DOI":"10.3233\/jad-2012-121543","volume":"33","author":"KE Davis","year":"2013","unstructured":"Davis, K. E., Easton, A., Eacott, M. J. & Gigg, J. Episodic-like memory for what-where-which occasion is selectively impaired in the 3xTgAD mouse model of Alzheimer\u2019s disease. Journal of Alzheimer\u2019s disease: JAD 33, 681\u2013698, doi: 10.3233\/jad-2012-121543 (2013).","journal-title":"Journal of Alzheimer\u2019s disease: JAD"},{"key":"BFsrep45561_CR118","doi-asserted-by":"publisher","first-page":"e0143767","DOI":"10.1371\/journal.pone.0143767","volume":"10","author":"AL Saive","year":"2015","unstructured":"Saive, A. L., Royet, J. P., Garcia, S., Thevenet, M. & Plailly, J. \u201cWhat-Where-Which\u201d Episodic Retrieval Requires Conscious Recollection and Is Promoted by Semantic Knowledge. PloS one 10, e0143767, doi: 10.1371\/journal.pone.0143767 (2015).","journal-title":"PloS one"},{"key":"BFsrep45561_CR119","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/s1474-4422(10)70112-5","volume":"9","author":"IT Lott","year":"2010","unstructured":"Lott, I. T. & Dierssen, M. Cognitive deficits and associated neurological complications in individuals with Down\u2019s syndrome. The Lancet. Neurology 9, 623\u2013633, doi: 10.1016\/s1474-4422(10)70112-5 (2010).","journal-title":"The Lancet. Neurology"},{"key":"BFsrep45561_CR120","unstructured":"O\u2019Keefe, J. & Nadel, L. The hippocampus as a cognitive map. (Oxford University Press, Oxford, UK, 1978)."},{"key":"BFsrep45561_CR121","doi-asserted-by":"crossref","first-page":"7535","DOI":"10.1523\/JNEUROSCI.18-18-07535.1998","volume":"18","author":"MB Moser","year":"1998","unstructured":"Moser, M. B. & Moser, E. I. Distributed encoding and retrieval of spatial memory in the hippocampus. The Journal of neuroscience: the official journal of the Society for Neuroscience 18, 7535\u20137542 (1998).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep45561_CR122","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.conb.2015.07.009","volume":"35","author":"S Tonegawa","year":"2015","unstructured":"Tonegawa, S., Pignatelli, M., Roy, D. S. & Ryan, T. J. Memory engram storage and retrieval. Curr Opin Neurobiol 35, 101\u2013109, doi: 10.1016\/j.conb.2015.07.009 (2015).","journal-title":"Curr Opin Neurobiol"},{"key":"BFsrep45561_CR123","doi-asserted-by":"crossref","unstructured":"Howell, M. D. & Gottschall, P. E. Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican. ASN neuro 4, doi: 10.1042\/an20110037 (2012).","DOI":"10.1042\/AN20110037"},{"key":"BFsrep45561_CR124","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/BF02361154","volume":"26","author":"ME Coussons-Read","year":"1996","unstructured":"Coussons-Read, M. E. & Crnic, L. S. Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: altered behavior in the elevated plus maze and open field. Behav Genet 26, 7\u201313 (1996).","journal-title":"Behav Genet"},{"key":"BFsrep45561_CR125","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0166-4328(97)81111-4","volume":"82","author":"GE Demas","year":"1996","unstructured":"Demas, G. E., Nelson, R. J., Krueger, B. K. & Yarowsky, P. J. Spatial memory deficits in segmental trisomic Ts65Dn mice. Behavioural brain research 82, 85\u201392 (1996).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR126","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.bbr.2005.04.016","volume":"163","author":"C Martinez-Cue","year":"2005","unstructured":"Martinez-Cue, C. et al. Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome. Behavioural brain research 163, 174\u2013185, doi: 10.1016\/j.bbr.2005.04.016 (2005).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR127","doi-asserted-by":"publisher","first-page":"e114521","DOI":"10.1371\/journal.pone.0114521","volume":"9","author":"LV Lysenko","year":"2014","unstructured":"Lysenko, L. V. et al. Monoacylglycerol lipase inhibitor JZL184 improves behavior and neural properties in Ts65Dn mice, a model of down syndrome. PloS one 9, e114521, doi: 10.1371\/journal.pone.0114521 (2014).","journal-title":"PloS one"},{"key":"BFsrep45561_CR128","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.nbd.2011.04.011","volume":"43","author":"M Faizi","year":"2011","unstructured":"Faizi, M. et al. Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down syndrome: activation of beta1-adrenergic receptor by xamoterol as a potential cognitive enhancer. Neurobiology of disease 43, 397\u2013413, doi: 10.1016\/j.nbd.2011.04.011 (2011).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR129","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1016\/j.freeradbiomed.2011.03.023","volume":"50","author":"M Shichiri","year":"2011","unstructured":"Shichiri, M. et al. alpha-Tocopherol suppresses lipid peroxidation and behavioral and cognitive impairments in the Ts65Dn mouse model of Down syndrome. Free radical biology & medicine 50, 1801\u20131811, doi: 10.1016\/j.freeradbiomed.2011.03.023 (2011).","journal-title":"Free radical biology & medicine"},{"key":"BFsrep45561_CR130","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.nbd.2014.06.001","volume":"70","author":"JA Ash","year":"2014","unstructured":"Ash, J. A. et al. Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice. Neurobiology of disease 70, 32\u201342, doi: 10.1016\/j.nbd.2014.06.001 (2014).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR131","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1002\/cne.23492","volume":"522","author":"CM Kelley","year":"2014","unstructured":"Kelley, C. M. et al. Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice. J Comp Neurol 522, 1390\u20131410, doi: 10.1002\/cne.23492 (2014).","journal-title":"J Comp Neurol"},{"key":"BFsrep45561_CR132","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1037\/a0019590","volume":"124","author":"J Moon","year":"2010","unstructured":"Moon, J. et al. Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of Down syndrome. Behav Neurosci 124, 346\u2013361, doi: 10.1037\/a0019590 (2010).","journal-title":"Behav Neurosci"},{"key":"BFsrep45561_CR133","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/brain\/awt340","volume":"137","author":"S Guidi","year":"2014","unstructured":"Guidi, S. et al. Prenatal pharmacotherapy rescues brain development in a Down\u2019s syndrome mouse model. Brain: a journal of neurology 137, 380\u2013401, doi: 10.1093\/brain\/awt340 (2014).","journal-title":"Brain: a journal of neurology"},{"key":"BFsrep45561_CR134","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/j.1750-3639.2012.00624.x","volume":"23","author":"S Guidi","year":"2013","unstructured":"Guidi, S. et al. Early pharmacotherapy with fluoxetine rescues dendritic pathology in the Ts65Dn mouse model of down syndrome. Brain pathology (Zurich, Switzerland) 23, 129\u2013143, doi: 10.1111\/j.1750-3639.2012.00624.x (2013).","journal-title":"Brain pathology (Zurich, Switzerland)"},{"key":"BFsrep45561_CR135","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.nbd.2014.12.005","volume":"74","author":"F Stagni","year":"2015","unstructured":"Stagni, F. et al. Long-term effects of neonatal treatment with fluoxetine on cognitive performance in Ts65Dn mice. Neurobiology of disease 74, 204\u2013218, doi: 10.1016\/j.nbd.2014.12.005 (2015).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR136","doi-asserted-by":"publisher","first-page":"e61689","DOI":"10.1371\/journal.pone.0061689","volume":"8","author":"F Stagni","year":"2013","unstructured":"Stagni, F. et al. Pharmacotherapy with fluoxetine restores functional connectivity from the dentate gyrus to field CA3 in the Ts65Dn mouse model of down syndrome. PloS one 8, e61689, doi: 10.1371\/journal.pone.0061689 (2013).","journal-title":"PloS one"},{"key":"BFsrep45561_CR137","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.neuroscience.2016.07.031","volume":"333","author":"F Stagni","year":"2016","unstructured":"Stagni, F. et al. Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome. Neuroscience 333, 277\u2013301, doi: 10.1016\/j.neuroscience.2016.07.031 (2016).","journal-title":"Neuroscience"},{"key":"BFsrep45561_CR138","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1080\/08035250500252609","volume":"94","author":"YJ Chen","year":"2005","unstructured":"Chen, Y. J. & Fang, P. C. Sensory evoked potentials in infants with Down syndrome. Acta paediatrica (Oslo, Norway: 1992) 94, 1615\u20131618, doi: 10.1080\/08035250500252609 (2005).","journal-title":"Acta paediatrica (Oslo, Norway: 1992)"},{"key":"BFsrep45561_CR139","first-page":"81","volume":"42","author":"C Toledo","year":"1999","unstructured":"Toledo, C., Alembik, Y., Aguirre Jaime, A. & Stoll, C. Growth curves of children with Down syndrome. Annales de genetique 42, 81\u201390 (1999).","journal-title":"Annales de genetique"},{"key":"BFsrep45561_CR140","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s10519-006-9057-8","volume":"36","author":"S Vicari","year":"2006","unstructured":"Vicari, S. Motor development and neuropsychological patterns in persons with Down syndrome. Behav Genet 36, 355\u2013364, doi: 10.1007\/s10519-006-9057-8 (2006).","journal-title":"Behav Genet"},{"key":"BFsrep45561_CR141","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.expneurol.2016.02.005","volume":"279","author":"JL Olmos-Serrano","year":"2016","unstructured":"Olmos-Serrano, J. L., Tyler, W. A., Cabral, H. J. & Haydar, T. F. Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome. Experimental neurology 279, 40\u201356, doi: 10.1016\/j.expneurol.2016.02.005 (2016).","journal-title":"Experimental neurology"},{"key":"BFsrep45561_CR142","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/ana.21120","volume":"62","author":"GK Murray","year":"2007","unstructured":"Murray, G. K., Jones, P. B., Kuh, D. & Richards, M. Infant developmental milestones and subsequent cognitive function. Ann Neurol 62, 128\u2013136, doi: 10.1002\/ana.21120 (2007).","journal-title":"Ann Neurol"},{"key":"BFsrep45561_CR143","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1469-7610.2005.01450.x","volume":"47","author":"GK Murray","year":"2006","unstructured":"Murray, G. K. et al. Infant motor development is associated with adult cognitive categorisation in a longitudinal birth cohort study. Journal of child psychology and psychiatry, and allied disciplines 47, 25\u201329, doi: 10.1111\/j.1469-7610.2005.01450.x (2006).","journal-title":"Journal of child psychology and psychiatry, and allied disciplines"},{"key":"BFsrep45561_CR144","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1469-8749.2005.tb01207.x","volume":"47","author":"A Taanila","year":"2005","unstructured":"Taanila, A., Murray, G. K., Jokelainen, J., Isohanni, M. & Rantakallio, P. Infant developmental milestones: a 31-year follow-up. Developmental medicine and child neurology 47, 581\u2013586 (2005).","journal-title":"Developmental medicine and child neurology"},{"key":"BFsrep45561_CR145","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1111\/jir.12189","volume":"59","author":"N Schott","year":"2015","unstructured":"Schott, N. & Holfelder, B. Relationship between motor skill competency and executive function in children with Down\u2019s syndrome. J Intellect Disabil Res 59, 860\u2013872, doi: 10.1111\/jir.12189 (2015).","journal-title":"J Intellect Disabil Res"},{"key":"BFsrep45561_CR146","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/1467-8624.00522","volume":"74","author":"BF Pennington","year":"2003","unstructured":"Pennington, B. F., Moon, J., Edgin, J., Stedron, J. & Nadel, L. The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child development 74, 75\u201393 (2003).","journal-title":"Child development"},{"key":"BFsrep45561_CR147","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0028-3932(96)00055-3","volume":"35","author":"GA Carlesimo","year":"1997","unstructured":"Carlesimo, G. A., Marotta, L. & Vicari, S. Long-term memory in mental retardation: evidence for a specific impairment in subjects with Down\u2019s syndrome. Neuropsychologia 35, 71\u201379 (1997).","journal-title":"Neuropsychologia"},{"key":"BFsrep45561_CR148","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nrn2303","volume":"9","author":"G Neves","year":"2008","unstructured":"Neves, G., Cooke, S. F. & Bliss, T. V. Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nature reviews. Neuroscience 9, 65\u201375, doi: 10.1038\/nrn2303 (2008).","journal-title":"Nature reviews. Neuroscience"},{"key":"BFsrep45561_CR149","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neuroscience.2008.07.025","volume":"156","author":"G Pollonini","year":"2008","unstructured":"Pollonini, G. et al. Abnormal expression of synaptic proteins and neurotrophin-3 in the Down syndrome mouse model Ts65Dn. Neuroscience 156, 99\u2013106, doi: 10.1016\/j.neuroscience.2008.07.025 (2008).","journal-title":"Neuroscience"},{"key":"BFsrep45561_CR150","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/cne.20337","volume":"480","author":"PV Belichenko","year":"2004","unstructured":"Belichenko, P. V. et al. Synaptic structural abnormalities in the Ts65Dn mouse model of Down Syndrome. J Comp Neurol 480, 281\u2013298, doi: 10.1002\/cne.20337 (2004).","journal-title":"J Comp Neurol"},{"key":"BFsrep45561_CR151","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.pneurobio.2004.08.001","volume":"74","author":"R Benavides-Piccione","year":"2004","unstructured":"Benavides-Piccione, R. et al. On dendrites in Down syndrome and DS murine models: a spiny way to learn. Progress in neurobiology 74, 111\u2013126, doi: 10.1016\/j.pneurobio.2004.08.001 (2004).","journal-title":"Progress in neurobiology"},{"key":"BFsrep45561_CR152","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0896-6273(00)81122-8","volume":"24","author":"R Janz","year":"1999","unstructured":"Janz, R. et al. Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 24, 687\u2013700 (1999).","journal-title":"Neuron"},{"key":"BFsrep45561_CR153","doi-asserted-by":"publisher","first-page":"e4606","DOI":"10.1371\/journal.pone.0004606","volume":"4","author":"F Guedj","year":"2009","unstructured":"Guedj, F. et al. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PloS one 4, e4606, doi: 10.1371\/journal.pone.0004606 (2009).","journal-title":"PloS one"},{"key":"BFsrep45561_CR154","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.nbd.2010.06.011","volume":"40","author":"D Toiber","year":"2010","unstructured":"Toiber, D. et al. Engineering DYRK1A overdosage yields Down syndrome-characteristic cortical splicing aberrations. Neurobiology of disease 40, 348\u2013359, doi: 10.1016\/j.nbd.2010.06.011 (2010).","journal-title":"Neurobiology of disease"},{"key":"BFsrep45561_CR155","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0166-4328(02)00082-7","volume":"139","author":"HA Bimonte-Nelson","year":"2003","unstructured":"Bimonte-Nelson, H. A., Hunter, C. L., Nelson, M. E. & Granholm, A. C. Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome. Behavioural brain research 139, 47\u201357 (2003).","journal-title":"Behavioural brain research"},{"key":"BFsrep45561_CR156","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neuron.2005.09.005","volume":"48","author":"A Barco","year":"2005","unstructured":"Barco, A. et al. Gene expression profiling of facilitated L-LTP in VP16-CREB mice reveals that BDNF is critical for the maintenance of LTP and its synaptic capture. Neuron 48, 123\u2013137, doi: 10.1016\/j.neuron.2005.09.005 (2005).","journal-title":"Neuron"},{"key":"BFsrep45561_CR157","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/85109","volume":"4","author":"GE Hardingham","year":"2001","unstructured":"Hardingham, G. E., Arnold, F. J. & Bading, H. Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nature neuroscience 4, 261\u2013267, doi: 10.1038\/85109 (2001).","journal-title":"Nature neuroscience"},{"key":"BFsrep45561_CR158","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1177\/0883073811405201","volume":"26","author":"S Ekstein","year":"2011","unstructured":"Ekstein, S., Glick, B., Weill, M., Kay, B. & Berger, I. Down syndrome and attention-deficit\/hyperactivity disorder (ADHD). Journal of child neurology 26, 1290\u20131295, doi: 10.1177\/0883073811405201 (2011).","journal-title":"Journal of child neurology"},{"key":"BFsrep45561_CR159","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1192\/bjp.149.2.156","volume":"149","author":"A Gath","year":"1986","unstructured":"Gath, A. & Gumley, D. Behaviour problems in retarded children with special reference to Down\u2019s syndrome. The British journal of psychiatry: the journal of mental science 149, 156\u2013161 (1986).","journal-title":"The British journal of psychiatry: the journal of mental science"},{"key":"BFsrep45561_CR160","first-page":"14","volume":"61","author":"JM Lesser","year":"2006","unstructured":"Lesser, J. M. & Hughes, S. Psychosis-related disturbances. Psychosis, agitation, and disinhibition in Alzheimer\u2019s disease: definitions and treatment options. Geriatrics 61, 14\u201320 (2006).","journal-title":"Geriatrics"},{"key":"BFsrep45561_CR161","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.bbr.2011.04.003","volume":"222","author":"TJ Reilly","year":"2011","unstructured":"Reilly, T. J. et al. Regional cerebral blood flow and aberrant motor behaviour in Alzheimer\u2019s disease. Behavioural brain research 222, 375\u2013379, doi: 10.1016\/j.bbr.2011.04.003 (2011).","journal-title":"Behavioural brain research"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep45561.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep45561","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/srep45561","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep45561.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T23:27:52Z","timestamp":1671838072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep45561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,3]]},"references-count":161,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,4,24]]}},"alternative-id":["BFsrep45561"],"URL":"https:\/\/doi.org\/10.1038\/srep45561","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,3]]},"assertion":[{"value":"5 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.I. has U.S. patents on CNTF small-molecule peptide mimetics for the treatment of AD and related conditions.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45561"}}