{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:10:15Z","timestamp":1793337015699,"version":"4.5.0"},"reference-count":157,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T00:00:00Z","timestamp":1512345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T00:00:00Z","timestamp":1512345600000},"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) is caused by the triplication of human chromosome 21 and represents the most frequent genetic cause of intellectual disability. The trisomic Ts65Dn mouse model of DS shows synaptic deficits and reproduces the essential cognitive disabilities of the human syndrome. Aerobic exercise improved various neurophysiological dysfunctions in Ts65Dn mice, including hippocampal synaptic deficits, by promoting synaptogenesis and neurotransmission at glutamatergic terminals. Most importantly, the same intervention also prompted the recovery of hippocampal adult neurogenesis and synaptic plasticity and restored cognitive performance in trisomic mice. Additionally, the expression of brain-derived neurotrophic factor (BDNF) was markedly decreased in the hippocampus of patients with DS. Since the positive effect of exercise was paralleled by increased BDNF expression in trisomic mice, we investigated the effectiveness of a BDNF-mimetic treatment with 7,8-dihydroxyflavone at alleviating intellectual disabilities in the DS model. Pharmacological stimulation of BDNF signaling rescued synaptic plasticity and memory deficits in Ts65Dn mice. Based on our findings, Ts65Dn mice benefit from interventions aimed at promoting brain plasticity, and we provide evidence that BDNF signaling represents a potentially new pharmacological target for treatments aimed at rescuing cognitive disabilities in patients with DS.<\/jats:p>","DOI":"10.1038\/s41598-017-17201-8","type":"journal-article","created":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T09:09:34Z","timestamp":1511860174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse model of Down syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"Martina","family":"Parrini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-7510","authenticated-orcid":false,"given":"Diego","family":"Ghezzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Deidda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian","family":"Medrihan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Castroflorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Alberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-3436","authenticated-orcid":false,"given":"Pietro","family":"Baldelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-057X","authenticated-orcid":false,"given":"Laura","family":"Cancedda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-4722","authenticated-orcid":false,"given":"Andrea","family":"Contestabile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,4]]},"reference":[{"key":"17201_CR1","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/nrn3314","volume":"13","author":"M Dierssen","year":"2012","unstructured":"Dierssen, M. Down syndrome: the brain in trisomic mode. Nature reviews. Neuroscience \n                           13, 844\u2013858 (2012).","journal-title":"Nature reviews. Neuroscience"},{"key":"17201_CR2","doi-asserted-by":"publisher","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 Dev \n                           74, 75\u201393 (2003).","journal-title":"Child Dev"},{"key":"17201_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1097\/YPG.0b013e32835fe426","volume":"23","author":"S Vicari","year":"2013","unstructured":"Vicari, S., Pontillo, M. & Armando, M. Neurodevelopmental and psychiatric issues in Down\u2019s syndrome: assessment and intervention. Psychiatr Genet \n                           23, 95\u2013107 (2013).","journal-title":"Psychiatr Genet"},{"key":"17201_CR4","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/B978-0-444-54299-1.00007-8","volume":"197","author":"JO Edgin","year":"2012","unstructured":"Edgin, J. O., Mason, G. M., Span\u00f2, G., Fern\u00e1ndez, A. & L. N. Human and mouse model cognitive phenotypes in Down syndrome: implications for assessment. Prog Brain Res \n                           197, 123\u2013151 (2012).","journal-title":"Prog Brain Res"},{"key":"17201_CR5","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 \n                           11, 177\u2013184 (1995).","journal-title":"Nat Genet"},{"key":"17201_CR6","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1172\/JCI64650","volume":"123","author":"A Contestabile","year":"2013","unstructured":"Contestabile, A. et al. Lithium rescues synaptic plasticity and memory in Down syndrome mice. J Clin Invest \n                           123, 348\u2013361 (2013).","journal-title":"J Clin Invest"},{"key":"17201_CR7","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1038\/sj.npp.1301535","volume":"33","author":"CSA Costa","year":"2007","unstructured":"Costa, C. S. A., Scott-McKean, J. J. & Stasko, M. R. Acute Injections of the NMDA Receptor Antagonist Memantine Rescue Performance Deficits of the Ts65Dn Mouse Model of Down Syndrome on a Fear Conditioning Test. Neuropsychopharmacology \n                           33, 1624\u20131632 (2007).","journal-title":"Neuropsychopharmacology"},{"key":"17201_CR8","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1007\/s00335-011-9356-0","volume":"22","author":"A Duchon","year":"2011","unstructured":"Duchon, A. et al. Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling down syndrome. Mamm Genome \n                           22, 674\u2013684, https:\/\/doi.org\/10.1007\/s00335-011-9356-0 (2011).","journal-title":"Mamm Genome"},{"key":"17201_CR9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.2147\/DDDT.S51476","volume":"9","author":"KJ Gardiner","year":"2014","unstructured":"Gardiner, K. J. Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations. Drug Des Devel Ther \n                           9, 103\u2013125 (2014).","journal-title":"Drug Des Devel Ther"},{"key":"17201_CR10","doi-asserted-by":"crossref","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 \n                           10, 411\u2013413 (2007).","journal-title":"Nature Neuroscience"},{"key":"17201_CR11","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. J Neurosci \n                           24, 8153\u20138160 (2004).","journal-title":"J Neurosci"},{"key":"17201_CR12","doi-asserted-by":"crossref","unstructured":"Hanson, J. E., Blank, M., Valenzuela, R. A., Garner, C. C. & Madison, D. V. The functional nature of synaptic circuitry is altered in area CA3 of the hippocampus in a mouse model of Down\u2019s syndrome. J. Physiology \n                           579 (2007).","DOI":"10.1113\/jphysiol.2006.114868"},{"key":"17201_CR13","doi-asserted-by":"crossref","unstructured":"Best, T. K., Cramer, N. P., Chakrabarti, L., Haydar, T. F. & Galdzicki, Z. Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome. Experimental Neurology (2012).","DOI":"10.1016\/j.expneurol.2011.11.033"},{"key":"17201_CR14","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.nbd.2011.10.009","volume":"45","author":"AM Kleschevnikov","year":"2012","unstructured":"Kleschevnikov, A. M. et al. Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis \n                           45, 683\u2013691 (2012).","journal-title":"Neurobiol Dis"},{"key":"17201_CR15","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nm.3827","volume":"21","author":"G Deidda","year":"2015","unstructured":"Deidda, G. et al. Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome. Nature Medicine \n                           21, 318\u2013326 (2015).","journal-title":"Nature Medicine"},{"key":"17201_CR16","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fncel.2017.00054","volume":"11","author":"A Contestabile","year":"2017","unstructured":"Contestabile, A., Magara, S. & Cancedda, L. The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome. Front Cell Neurosci \n                           11, 54 (2017).","journal-title":"Front Cell Neurosci"},{"key":"17201_CR17","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 \n                           8, e61689 (2013).","journal-title":"PLoS One"},{"key":"17201_CR18","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1177\/0269881111405366","volume":"25","author":"J Braudeau","year":"2011","unstructured":"Braudeau, J. et al. Specific targeting of the GABA-A receptor alpha5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice. Journal of psychopharmacology \n                           25, 1030\u20131042, https:\/\/doi.org\/10.1177\/0269881111405366 (2011).","journal-title":"Journal of psychopharmacology"},{"key":"17201_CR19","doi-asserted-by":"publisher","first-page":"3953","DOI":"10.1523\/JNEUROSCI.1203-12.2013","volume":"33","author":"C Martinez-Cue","year":"2013","unstructured":"Martinez-Cue, C. et al. Reducing GABAA alpha5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome. J Neurosci \n                           33, 3953\u20133966, https:\/\/doi.org\/10.1523\/JNEUROSCI.1203-12.2013 (2013).","journal-title":"J Neurosci"},{"key":"17201_CR20","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. Neurosci Lett \n                           382, 317\u2013322 (2005).","journal-title":"Neurosci Lett"},{"key":"17201_CR21","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. Exp Neurol \n                           200, 256\u2013261 (2006).","journal-title":"Exp Neurol"},{"key":"17201_CR22","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.arr.2012.01.007","volume":"11","author":"MP Mattson","year":"2012","unstructured":"Mattson, M. P. Evolutionary aspects of human exercise\u2013born to run purposefully. Ageing research reviews \n                           11, 347\u2013352 (2012).","journal-title":"Ageing research reviews"},{"key":"17201_CR23","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0166-2236(02)02143-4","volume":"25","author":"CW Cotman","year":"2002","unstructured":"Cotman, C. W. & Berchtold, N. C. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci \n                           25, 295\u2013301 (2002).","journal-title":"Trends Neurosci"},{"key":"17201_CR24","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.tins.2008.12.007","volume":"32","author":"H van Praag","year":"2009","unstructured":"van Praag, H. Exercise and the brain: something to chew on. Trends Neurosci \n                           32, 283\u2013290 (2009).","journal-title":"Trends Neurosci"},{"key":"17201_CR25","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nrn2298","volume":"9","author":"CH Hillman","year":"2008","unstructured":"Hillman, C. H., Erickson, K. I. & Kramer, A. F. Be smart, exercise your heart: exercise effects on brain and cognition. Nature reviews. Neuroscience \n                           9, 58\u201365 (2008).","journal-title":"Nature reviews. Neuroscience"},{"key":"17201_CR26","doi-asserted-by":"crossref","unstructured":"Intlekofer, K. A. & Cotman, C. W. Exercise counteracts declining hippocampal function in aging and Alzheimer\u2019s disease. Neurobiol Dis (2012).","DOI":"10.1016\/j.nbd.2012.06.011"},{"key":"17201_CR27","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.neuroscience.2010.02.050","volume":"167","author":"NC Berchtold","year":"2010","unstructured":"Berchtold, N. C., Castello, N. & Cotman, C. W. Exercise and time-dependent benefits to learning and memory. Neuroscience \n                           167, 588\u2013597 (2010).","journal-title":"Neuroscience"},{"key":"17201_CR28","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1152\/japplphysiol.00210.2011","volume":"111","author":"MW Voss","year":"2011","unstructured":"Voss, M. W., Nagamatsu, L. S., Liu-Ambrose, T. & Kramer, A. F. Exercise, brain, and cognition across the life span. Journal of applied physiology \n                           111, 1505\u20131513 (2011).","journal-title":"Journal of applied physiology"},{"key":"17201_CR29","doi-asserted-by":"publisher","first-page":"5638","DOI":"10.1073\/pnas.0611721104","volume":"104","author":"AC Pereira","year":"2007","unstructured":"Pereira, A. C. et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA \n                           104, 5638\u20135643 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17201_CR30","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1073\/pnas.1015950108","volume":"108","author":"KI Erickson","year":"2011","unstructured":"Erickson, K. I. et al. Exercise training increases size of hippocampus and improves memory. PNAS \n                           108, 3017\u20133322 (2011).","journal-title":"PNAS"},{"key":"17201_CR31","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1177\/1073858410397054","volume":"18","author":"KI Erickson","year":"2012","unstructured":"Erickson, K. I., Miller, D. L. & Roecklein, K. A. The aging hippocampus: interactions between exercise, depression, and BDNF. The Neuroscientist: a review journal bringing neurobiology, neurology and psychiatry \n                           18, 82\u201397, https:\/\/doi.org\/10.1177\/1073858410397054 (2012).","journal-title":"The Neuroscientist: a review journal bringing neurobiology, neurology and psychiatry"},{"key":"17201_CR32","first-page":"533","volume":"61","author":"JA Zoladz","year":"2010","unstructured":"Zoladz, J. A. & Pilc, A. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. Journal of physiology and pharmacology: an official journal of the Polish Physiological Society \n                           61, 533\u2013541 (2010).","journal-title":"Journal of physiology and pharmacology: an official journal of the Polish Physiological Society"},{"key":"17201_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22119","author":"MW Voss","year":"2012","unstructured":"Voss, M. W. et al. The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one-year exercise intervention. Human brain mapping. https:\/\/doi.org\/10.1002\/hbm.22119 (2012).","journal-title":"Human brain mapping"},{"key":"17201_CR34","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1385\/JMN:20:3:213","volume":"20","author":"AF Kramer","year":"2003","unstructured":"Kramer, A. F. et al. Enhancing brain and cognitive function of older adults through fitness training. J Mol Neurosci \n                           20, 213\u2013221 (2003).","journal-title":"J Mol Neurosci"},{"key":"17201_CR35","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1093\/gerona\/58.2.M176","volume":"58","author":"SJ Colcombe","year":"2003","unstructured":"Colcombe, S. J. et al. Aerobic fitness reduces brain tissue loss in aging humans. The journals of gerontology. Series A, Biological sciences and medical sciences \n                           58, 176\u2013180 (2003).","journal-title":"Series A, Biological sciences and medical sciences"},{"key":"17201_CR36","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1097\/PSY.0b013e3181d14633","volume":"72","author":"PJ Smith","year":"2010","unstructured":"Smith, P. J. et al. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosomatic medicine \n                           72, 239\u2013252 (2010).","journal-title":"Psychosomatic medicine"},{"key":"17201_CR37","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/1467-9280.t01-1-01430","volume":"14","author":"S Colcombe","year":"2003","unstructured":"Colcombe, S. & Kramer, A. F. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychological science \n                           14, 125\u2013130 (2003).","journal-title":"Psychological science"},{"key":"17201_CR38","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s12017-008-8028-z","volume":"10","author":"H van Praag","year":"2008","unstructured":"van Praag, H. Neurogenesis and exercise: past and future directions. Neuromolecular Med. \n                           10, 128\u2013140 (2008).","journal-title":"Neuromolecular Med."},{"key":"17201_CR39","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.bbr.2012.05.012","volume":"233","author":"MM Herting","year":"2012","unstructured":"Herting, M. M. & Nagel, B. J. Aerobic fitness relates to learning on a virtual Morris Water Task and hippocampal volume in adolescents. Behav Brain Res \n                           233, 517\u2013525 (2012).","journal-title":"Behav Brain Res"},{"key":"17201_CR40","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/373109a0","volume":"373","author":"SA Neeper","year":"1995","unstructured":"Neeper, S. A., Gomez-Pinilla, F., Choi, J. & Cotman, C. Exercise and brain neurotrophins. Nature \n                           373, 109 (1995).","journal-title":"Nature"},{"key":"17201_CR41","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.neuroscience.2005.03.026","volume":"133","author":"NC Berchtold","year":"2005","unstructured":"Berchtold, N. C., Chinn, G., Chou, M., Kesslak, J. P. & Cotman, C. W. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience \n                           133, 853\u2013861 (2005).","journal-title":"Neuroscience"},{"key":"17201_CR42","doi-asserted-by":"crossref","first-page":"8680","DOI":"10.1523\/JNEUROSCI.1731-05.2005","volume":"25","author":"H van Praag","year":"2005","unstructured":"van Praag, H., Shubert, T., Zhao, C. & Gage, F. H. Exercise Enhances Learning and Hippocampal Neurogenesisin Aged Mice. Journal of Nuroscience \n                           25, 8680\u20138685 (2005).","journal-title":"Journal of Nuroscience"},{"key":"17201_CR43","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1002\/hipo.20157","volume":"16","author":"AK Olson","year":"2006","unstructured":"Olson, A. K., Eadie, B. D., Ernst, C. & Christie, B. R. Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus \n                           16, 250\u2013260 (2006).","journal-title":"Hippocampus"},{"key":"17201_CR44","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.neuroscience.2003.09.029","volume":"124","author":"J Farmer","year":"2004","unstructured":"Farmer, J. et al. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience \n                           124, 71\u201379 (2004).","journal-title":"Neuroscience"},{"key":"17201_CR45","doi-asserted-by":"publisher","first-page":"e24263","DOI":"10.1371\/journal.pone.0024263","volume":"6","author":"SY Yau","year":"2011","unstructured":"Yau, S. Y. et al. Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats. Plos One \n                           6, e24263 (2011).","journal-title":"Plos One"},{"key":"17201_CR46","doi-asserted-by":"crossref","unstructured":"van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci, 266-270 (1999).","DOI":"10.1038\/6368"},{"key":"17201_CR47","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1111\/j.1460-9568.2004.03720.x","volume":"20","author":"S Vaynman","year":"2004","unstructured":"Vaynman, S., Ying, Z. & Gomez-Pinilla, F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. European Journal of Neuroscience \n                           20, 2580\u20132590 (2004).","journal-title":"European Journal of Neuroscience"},{"key":"17201_CR48","doi-asserted-by":"publisher","first-page":"13427","DOI":"10.1073\/pnas.96.23.13427","volume":"96","author":"H van Praag","year":"1999","unstructured":"van Praag, H., Christie, B. R., Sejnowski, T. J. & Gage, F. H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA \n                           96, 13427\u201313431 (1999).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17201_CR49","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.neuron.2008.06.023","volume":"59","author":"Y Li","year":"2008","unstructured":"Li, Y. et al. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron \n                           59, 399\u2013412 (2008).","journal-title":"Neuron"},{"key":"17201_CR50","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1111\/j.1460-9568.2008.06524.x","volume":"28","author":"F Gomez-Pinilla","year":"2008","unstructured":"Gomez-Pinilla, F., Vaynman, S. & Ying, Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci \n                           28, 2278\u20132287 (2008).","journal-title":"Eur J Neurosci"},{"key":"17201_CR51","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.semcdb.2011.07.002","volume":"22","author":"P Bekinschtein","year":"2011","unstructured":"Bekinschtein, P., Oomen, C. A., Saksida, L. M. & Bussey, T. J. Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol \n                           22, 536\u2013542 (2011).","journal-title":"Semin Cell Dev Biol"},{"key":"17201_CR52","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1002\/hipo.20631","volume":"19","author":"EW Griffin","year":"2009","unstructured":"Griffin, E. W., Bechara, R. G., Birch, A. M. & Kelly, A. M. Exercise enhances hippocampal-dependent learning in the rat: evidence for a BDNF-related mechanism. Hippocampus \n                           19, 973\u2013980 (2009).","journal-title":"Hippocampus"},{"key":"17201_CR53","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/381706a0","volume":"381","author":"A Figurov","year":"1996","unstructured":"Figurov, A., Pozzo-Miller, L. D., Olafsson, P., Wang, T. & Lu, B. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature \n                           381, 706\u2013709 (1996).","journal-title":"Nature"},{"key":"17201_CR54","doi-asserted-by":"publisher","first-page":"8856","DOI":"10.1073\/pnas.92.19.8856","volume":"92","author":"M Korte","year":"1995","unstructured":"Korte, M. et al. Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA \n                           92, 8856\u20138860 (1995).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17201_CR55","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/S0896-6273(00)80140-3","volume":"16","author":"SL Patterson","year":"1996","unstructured":"Patterson, S. L. et al. Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron \n                           16, 1137\u20131145 (1996).","journal-title":"Neuron"},{"key":"17201_CR56","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1111\/j.1460-9568.1997.tb01687.x","volume":"9","author":"S Linnarsson","year":"1997","unstructured":"Linnarsson, S., Bjorklund, A. & Ernfors, P. Learning deficit in BDNF mutant mice. Eur J Neurosci \n                           9, 2581\u20132587 (1997).","journal-title":"Eur J Neurosci"},{"key":"17201_CR57","doi-asserted-by":"crossref","first-page":"7116","DOI":"10.1523\/JNEUROSCI.20-18-07116.2000","volume":"20","author":"M Mizuno","year":"2000","unstructured":"Mizuno, M., Yamada, K., Olariu, A., Nawa, H. & Nabeshima, T. Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J Neurosci \n                           20, 7116\u20137121 (2000).","journal-title":"J Neurosci"},{"key":"17201_CR58","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S0896-6273(00)80853-3","volume":"24","author":"L Minichiello","year":"1999","unstructured":"Minichiello, L. et al. Essential role for TrkB receptors in hippocampus-mediated learning. Neuron \n                           24, 401\u2013414 (1999).","journal-title":"Neuron"},{"key":"17201_CR59","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/sj.mp.4001957","volume":"12","author":"SA Heldt","year":"2007","unstructured":"Heldt, S. A., Stanek, L., Chhatwal, J. P. & Ressler, K. J. Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol Psychiatry \n                           12, 656\u2013670 (2007).","journal-title":"Mol Psychiatry"},{"key":"17201_CR60","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/hipo.10035","volume":"12","author":"M Alonso","year":"2002","unstructured":"Alonso, M. et al. BDNF-triggered events in the rat hippocampus are required for both short- and long-term memory formation. Hippocampus \n                           12, 551\u2013560 (2002).","journal-title":"Hippocampus"},{"key":"17201_CR61","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1126\/science.1095760","volume":"304","author":"JL Lee","year":"2004","unstructured":"Lee, J. L., Everitt, B. J. & Thomas, K. L. Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science \n                           304, 839\u2013843 (2004).","journal-title":"Science"},{"key":"17201_CR62","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1073\/pnas.0711863105","volume":"105","author":"P Bekinschtein","year":"2008","unstructured":"Bekinschtein, P. et al. BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci USA \n                           105, 2711\u20132716 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17201_CR63","doi-asserted-by":"publisher","first-page":"15570","DOI":"10.1073\/pnas.0803702105","volume":"105","author":"M Bergami","year":"2008","unstructured":"Bergami, M. et al. Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior. Proc Natl Acad Sci USA \n                           105, 15570\u201315575 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17201_CR64","doi-asserted-by":"publisher","first-page":"14318","DOI":"10.1523\/JNEUROSCI.0709-12.2012","volume":"32","author":"EG Waterhouse","year":"2012","unstructured":"Waterhouse, E. G. et al. BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission. J Neurosci \n                           32, 14318\u201314330 (2012).","journal-title":"J Neurosci"},{"key":"17201_CR65","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.nbd.2015.07.014","volume":"82","author":"T Begenisic","year":"2015","unstructured":"Begenisic, T., Sansevero, G., Baroncelli, L., Cioni, G. & A. S. Early environmental therapy rescues brain development in a mouse model of Down syndrome. Neurobiol Dis \n                           82, 409\u2013419 (2015).","journal-title":"Neurobiol Dis"},{"key":"17201_CR66","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. J Neurosci \n                           32, 9217\u20139227 (2012).","journal-title":"J Neurosci"},{"key":"17201_CR67","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.bbr.2010.03.036","volume":"221","author":"J Lockrow","year":"2011","unstructured":"Lockrow, J., Bogera, H., Bimonte-Nelson, H. & Granholm, A. C. Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome. Behavioural Brain Research \n                           221, 610\u2013622 (2011).","journal-title":"Behavioural Brain Research"},{"key":"17201_CR68","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.bbr.2013.02.018","volume":"245","author":"RG Bechara","year":"2013","unstructured":"Bechara, R. G. & Kelly, A. M. Exercise improves object recognition memory and induces BDNF expression and cell proliferation in cognitively enriched rats. Behav Brain Res \n                           245, 96\u2013100 (2013).","journal-title":"Behav Brain Res"},{"key":"17201_CR69","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.neuroscience.2011.07.071","volume":"194","author":"ME Hopkins","year":"2011","unstructured":"Hopkins, M. E., Nitecki, R. & Bucci, D. J. Physical exercise during adolescence versus adulthood: differential effects on object recognition memory and brain-derived neurotrophic factor levels. Neuroscience \n                           194, 84\u201394 (2011).","journal-title":"Neuroscience"},{"key":"17201_CR70","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/nrn2822","volume":"11","author":"W Deng","year":"2010","unstructured":"Deng, W., Aimone, J. B. & Gage, F. H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nature reviews. Neuroscience \n                           11, 339\u2013350 (2010).","journal-title":"Nature reviews. Neuroscience"},{"key":"17201_CR71","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/386493a0","volume":"386","author":"G Kempermann","year":"1997","unstructured":"Kempermann, G., Kuhn, H. G. & Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature \n                           386, 493\u2013495 (1997).","journal-title":"Nature"},{"key":"17201_CR72","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1523\/JNEUROSCI.17-10-03727.1997","volume":"17","author":"JM Parent","year":"1997","unstructured":"Parent, J. M. et al. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci \n                           17, 3727\u20133738 (1997).","journal-title":"J Neurosci"},{"key":"17201_CR73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cne.10874","volume":"467","author":"JP Brown","year":"2003","unstructured":"Brown, J. P. et al. Transient expression of doublecortin during adult neurogenesis. J Comp Neurol \n                           467, 1\u201310 (2003).","journal-title":"J Comp Neurol"},{"key":"17201_CR74","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1152\/jn.2001.85.6.2423","volume":"85","author":"JS Snyder","year":"2001","unstructured":"Snyder, J. S., Kee, N. & Wojtowicz, J. M. Effects of Adult Neurogenesis on Synaptic Plasticity in the Rat Dentate Gyrus. J Neurophysiol \n                           85, 2423\u20132431 (2001).","journal-title":"J Neurophysiol"},{"key":"17201_CR75","doi-asserted-by":"publisher","first-page":"17501","DOI":"10.1073\/pnas.0607207103","volume":"103","author":"MD Saxe","year":"2006","unstructured":"Saxe, M. D. et al. Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. PNAS \n                           103, 17501\u201317506 (2006).","journal-title":"PNAS"},{"key":"17201_CR76","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nature09817","volume":"472","author":"A Sahay","year":"2011","unstructured":"Sahay, A. et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature \n                           472, 466\u2013470, https:\/\/doi.org\/10.1038\/nature09817 (2011).","journal-title":"Nature"},{"key":"17201_CR77","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.neuron.2007.05.002","volume":"54","author":"S Ge","year":"2007","unstructured":"Ge, S., Yang, C., Hsu, K., Ming, G. & Song, H. A Critical Period for Enhanced Synaptic Plasticity in Newly Generated Neurons of the Adult Brain. Neuron \n                           54, 559\u2013566 (2007).","journal-title":"Neuron"},{"key":"17201_CR78","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/nn.2600","volume":"13","author":"L Chakrabarti","year":"2010","unstructured":"Chakrabarti, L. et al. Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat Neurosci \n                           13, 927\u2013934 (2010).","journal-title":"Nat Neurosci"},{"key":"17201_CR79","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1101\/lm.2283011","volume":"18","author":"T Kobilo","year":"2011","unstructured":"Kobilo, T. et al. Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learn Mem \n                           18, 605\u2013609 (2011).","journal-title":"Learn Mem"},{"key":"17201_CR80","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1002\/jnr.21139","volume":"85","author":"T Aid","year":"2007","unstructured":"Aid, T., Kazantseva, A., Piirsoo, M., Palm, K. & Timmusk, T. Mouse and Rat BDNF Gene Structure and Expression Revisited. Journal of Neuroscience Research \n                           85, 525\u2013535 (2007).","journal-title":"Journal of Neuroscience Research"},{"key":"17201_CR81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2005.10.004","volume":"1067","author":"Q Liu","year":"2006","unstructured":"Liu, Q. et al. Rodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine. BRAIN RESEARCH \n                           1067, 1\u20131 2 (2006).","journal-title":"BRAIN RESEARCH"},{"key":"17201_CR82","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0169-328X(98)00222-8","volume":"61","author":"HS Oliff","year":"1998","unstructured":"Oliff, H. S., Berchtold, N. C., Isackson, P. & Cotman, C. W. Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. Brain Res Mol Brain Res \n                           61, 147\u2013153 (1998).","journal-title":"Brain Res Mol Brain Res"},{"key":"17201_CR83","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1159\/000346920","volume":"91","author":"X Liu","year":"2013","unstructured":"Liu, X. et al. O-Methylated Metabolite of 7,8-Dihydroxyflavone Activates TrkB Receptor and Displays Antidepressant Activity. Pharmacology \n                           91, 185\u2013200 (2013).","journal-title":"Pharmacology"},{"key":"17201_CR84","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1073\/pnas.0913572107","volume":"107","author":"SW Jang","year":"2010","unstructured":"Jang, S. W. et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci USA \n                           107, 2687\u20132692 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17201_CR85","doi-asserted-by":"publisher","first-page":"8274","DOI":"10.1021\/jm101206p","volume":"53","author":"X Liu","year":"2010","unstructured":"Liu, X. et al. A Synthetic 7,8-Dihydroxyflavone Derivative Promotes Neurogenesis and Exhibits Potent Antidepressant Effect. J Med Chem \n                           53, 8274\u20138286 (2010).","journal-title":"J Med Chem"},{"key":"17201_CR86","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1176\/appi.ajp.2010.10030326","volume":"168","author":"R Andero","year":"2011","unstructured":"Andero, R. et al. Effect of 7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning. Am J Psychiatry \n                           168, 163\u2013172 (2011).","journal-title":"Am J Psychiatry"},{"key":"17201_CR87","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1093\/hmg\/ddt098","volume":"22","author":"M Jiang","year":"2013","unstructured":"Jiang, M. et al. Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington\u2019s disease. Hum Mol Genet \n                           22, 2462\u20132470 (2013).","journal-title":"Hum Mol Genet"},{"key":"17201_CR88","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/npp.2013.243","volume":"39","author":"Z Zhang","year":"2014","unstructured":"Zhang, Z. et al. 7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer\u2019s disease. Neuropsychopharmacology \n                           39, 638\u2013650 (2014).","journal-title":"Neuropsychopharmacology"},{"key":"17201_CR89","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/npp.2011.191","volume":"37","author":"L Devi","year":"2012","unstructured":"Devi, L. & Ohno, M. 7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer\u2019s disease. Neuropsychopharmacology \n                           37, 434\u2013444 (2012).","journal-title":"Neuropsychopharmacology"},{"key":"17201_CR90","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3389\/fnagi.2016.00287","volume":"8","author":"Y Tan","year":"2016","unstructured":"Tan, Y. et al. 7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice. Front Aging Neurosci \n                           8, 287, https:\/\/doi.org\/10.3389\/fnagi.2016.00287 (2016).","journal-title":"Front Aging Neurosci"},{"key":"17201_CR91","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neulet.2016.10.035","volume":"635","author":"MW Zhang","year":"2016","unstructured":"Zhang, M. W., Zhang, S. F., Li, Z. H. & Han, F. 7,8-Dihydroxyflavone reverses the depressive symptoms in mouse chronic mild stress. Neurosci Lett \n                           635, 33\u201338, https:\/\/doi.org\/10.1016\/j.neulet.2016.10.035 (2016).","journal-title":"Neurosci Lett"},{"key":"17201_CR92","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1111\/jnc.13432","volume":"136","author":"L Gao","year":"2016","unstructured":"Gao, L. et al. TrkB activation by 7,8-dihydroxyflavone increases synapse AMPA subunits and ameliorates spatial memory deficits in a mouse model of Alzheimer\u2019s disease. J Neurochem \n                           136, 620\u2013636 (2016).","journal-title":"J Neurochem"},{"key":"17201_CR93","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.bbadis.2015.01.018","volume":"1852","author":"R Agrawal","year":"2015","unstructured":"Agrawal, R. et al. Flavonoid derivative 7,8-DHF attenuates TBI pathology via TrkB activation. Biochim Biophys Acta \n                           1852, 862\u2013872, https:\/\/doi.org\/10.1016\/j.bbadis.2015.01.018 (2015).","journal-title":"Biochim Biophys Acta"},{"key":"17201_CR94","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.neuroscience.2014.12.080","volume":"290","author":"MD Sconce","year":"2015","unstructured":"Sconce, M. D., Churchill, M. J., Moore, C. & Meshul, C. K. Intervention with 7,8-dihydroxyflavone blocks further striatal terminal loss and restores motor deficits in a progressive mouse model of Parkinson\u2019s disease. Neuroscience \n                           290, 454\u2013471, https:\/\/doi.org\/10.1016\/j.neuroscience.2014.12.080 (2015).","journal-title":"Neuroscience"},{"key":"17201_CR95","doi-asserted-by":"publisher","first-page":"16207","DOI":"10.1523\/JNEUROSCI.0747-14.2014","volume":"34","author":"YH Hsiao","year":"2014","unstructured":"Hsiao, Y. H., Hung, H. C., Chen, S. H. & Gean, P. W. Social interaction rescues memory deficit in an animal model of Alzheimer\u2019s disease by increasing BDNF-dependent hippocampal neurogenesis. J Neurosci \n                           34, 16207\u201316219, https:\/\/doi.org\/10.1523\/JNEUROSCI.0747-14.2014 (2014).","journal-title":"J Neurosci"},{"key":"17201_CR96","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/1098-2779(2000)6:2<84::AID-MRDD2>3.0.CO;2-P","volume":"6","author":"RS Chapman","year":"2000","unstructured":"Chapman, R. S. & Hesketh, L. J. Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Disabil Res Rev \n                           6, 84\u201395 (2000).","journal-title":"Ment Retard Dev Disabil Res Rev"},{"key":"17201_CR97","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1086\/338915","volume":"70","author":"CJ Epstein","year":"2002","unstructured":"Epstein, C. J. 2001 William Allan Award Address. From Down syndrome to the \u201chuman\u201d in \u201chuman genetics\u201d. Am J Hum Genet \n                           70, 300\u2013313 (2002).","journal-title":"Am J Hum Genet"},{"key":"17201_CR98","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/S0140-6736(03)12987-X","volume":"361","author":"NJ Roizen","year":"2003","unstructured":"Roizen, N. J. & Patterson, D. Down\u2019s syndrome. Lancet \n                           361, 1281\u20131289 (2003).","journal-title":"Lancet"},{"key":"17201_CR99","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1111\/j.1651-2227.2004.tb03059.x","volume":"93","author":"S Vicari","year":"2004","unstructured":"Vicari, S. Memory development and intellectual disabilities. Acta Paediatr Suppl \n                           93, 60\u201363, discussion 63\u201364 (2004).","journal-title":"Acta Paediatr Suppl"},{"key":"17201_CR100","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/S0028-3932(99)00081-0","volume":"38","author":"S Vicari","year":"2000","unstructured":"Vicari, S., Bellucci, S. & Carlesimo, G. A. Implicit and explicit memory: a functional dissociation in persons with Down syndrome. Neuropsychologia \n                           38, 240\u2013251 (2000).","journal-title":"Neuropsychologia"},{"key":"17201_CR101","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1017\/S0012162205000599","volume":"47","author":"S Vicari","year":"2005","unstructured":"Vicari, S., Bellucci, S. & Carlesimo, G. A. Visual and spatial long-term memory: differential pattern of impairments in Williams and Down syndromes. Dev Med Child Neurol \n                           47, 305\u2013311 (2005).","journal-title":"Dev Med Child Neurol"},{"issue":"Pt 3","key":"17201_CR102","first-page":"227","volume":"27","author":"PE Sylvester","year":"1983","unstructured":"Sylvester, P. E. The hippocampus in Down\u2019s syndrome. J Ment Defic Res \n                           27(Pt 3), 227\u2013236 (1983).","journal-title":"J Ment Defic Res"},{"key":"17201_CR103","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1176\/ajp.156.4.564","volume":"156","author":"EH Aylward","year":"1999","unstructured":"Aylward, E. H. et al. MRI volumes of the hippocampus and amygdala in adults with Down\u2019s syndrome with and without dementia. Am J Psychiatry \n                           156, 564\u2013568 (1999).","journal-title":"Am J Psychiatry"},{"key":"17201_CR104","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1176\/appi.ajp.158.10.1659","volume":"158","author":"JD Pinter","year":"2001","unstructured":"Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T. & Reiss, A. L. Neuroanatomy of Down\u2019s syndrome: a high-resolution MRI study. Am J Psychiatry \n                           158, 1659\u20131665 (2001).","journal-title":"Am J Psychiatry"},{"key":"17201_CR105","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1176\/appi.ajp.159.1.74","volume":"159","author":"JS Krasuski","year":"2002","unstructured":"Krasuski, J. S., Alexander, G. E., Horwitz, B., rapoport, S. I. & Schapiro, M. B. Relation of Medial Temporal Lobe Volumes to Age and Memory Function in Nondemented Adults With Down\u2019s Syndrome: Implications for the Prodromal Phase of Alzheimer\u2019s Disease. Am J Psychiatry \n                           159, 74\u201381 (2002).","journal-title":"Am J Psychiatry"},{"key":"17201_CR106","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/mnfr.201300325","volume":"58","author":"R De la Torre","year":"2014","unstructured":"De la Torre, R. et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Molecular nutrition & food research \n                           58, 278\u2013288 (2014).","journal-title":"Molecular nutrition & food research"},{"key":"17201_CR107","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 Pathol \n                           23, 129\u2013143 (2013).","journal-title":"Brain Pathol"},{"key":"17201_CR108","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 \n                           14, 401\u2013416 (2013).","journal-title":"Nature reviews. Neuroscience"},{"key":"17201_CR109","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1016\/j.neuroscience.2010.09.043","volume":"171","author":"MV Llorens-Martin","year":"2010","unstructured":"Llorens-Martin, M. V. et al. Effects of voluntary physical exercise on adult hippocampal neurogenesis and behavior of Ts65Dn mice, a model of Down syndrome. Neuroscience \n                           171, 1228\u20131240 (2010).","journal-title":"Neuroscience"},{"key":"17201_CR110","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.expneurol.2012.11.022","volume":"240","author":"E Kida","year":"2013","unstructured":"Kida, E., Rabe, A., Walus, M., Albertini, G. & Golabek, A. A. Long-term running alleviates some behavioral and molecular abnormalities in Down syndrome mouse model Ts65Dn. Exp Neurol \n                           240, 178\u2013189 (2013).","journal-title":"Exp Neurol"},{"key":"17201_CR111","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 \n                           58, 92\u2013101 (2013).","journal-title":"Neurobiology of Disease"},{"key":"17201_CR112","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/jpi.12097","volume":"56","author":"A Corrales","year":"2013","unstructured":"Corrales, A. et al. Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome. J Pineal Res \n                           56, 51\u201361 (2013).","journal-title":"J Pineal Res"},{"key":"17201_CR113","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. J. Neuroscience \n                           27, 11483\u201311495 (2007).","journal-title":"J. Neuroscience"},{"key":"17201_CR114","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.brainres.2004.06.075","volume":"1022","author":"AM Kurt","year":"2004","unstructured":"Kurt, A. M., Kafa, I. M., Dierssen, M. & Davies, C. D. Deficits of neuronal density in CA1 and synaptic density in the dentate gyrus, CA3 and CA1, in a mouse model of Down syndrome. Brain Res \n                           1022, 101\u2013109 (2004).","journal-title":"Brain Res"},{"key":"17201_CR115","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0006-8993(00)01984-3","volume":"858","author":"MA Kurt","year":"2000","unstructured":"Kurt, M. A., Davies, D. C., Kidd, M., Dierssen, M. & Florez, J. Synaptic deficit in the temporal cortex of partial trisomy 16 (Ts65Dn) mice. Brain Res \n                           858, 191\u2013197 (2000).","journal-title":"Brain Res"},{"key":"17201_CR116","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3233\/JAD-2010-100240","volume":"21","author":"N Rueda","year":"2010","unstructured":"Rueda, N. et al. Memantine normalizes several phenotypic features in the Ts65Dn mouse model of Down syndrome. J Alzheimers Dis \n                           21, 277\u2013290 (2010).","journal-title":"J Alzheimers Dis"},{"key":"17201_CR117","doi-asserted-by":"publisher","first-page":"e106572","DOI":"10.1371\/journal.pone.0106572","volume":"9","author":"S Garc\u00eda-Cerro","year":"2014","unstructured":"Garc\u00eda-Cerro, S. et al. Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome. PLoS One \n                           9, e106572 (2014).","journal-title":"PLoS One"},{"key":"17201_CR118","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jsb.2009.10.014","volume":"172","author":"T Branco","year":"2010","unstructured":"Branco, T., Marra, V. & Staras, K. Examining size-strength relationships at hippocampal synapses using an ultrastructural measurement of synaptic release probability. J Struct Biol \n                           172, 203\u2013210 (2010).","journal-title":"J Struct Biol"},{"key":"17201_CR119","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S0896-6273(01)00500-1","volume":"32","author":"VN Murthy","year":"2001","unstructured":"Murthy, V. N., Schikorski, T., Stevens, C. F. & Zhu, Y. Inactivity Produces Increases in Neurotransmitter Release and Synapse Size. Neuron \n                           32, 673\u2013682 (2001).","journal-title":"Neuron"},{"key":"17201_CR120","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1002\/cne.21895","volume":"512","author":"PV Belichenko","year":"2009","unstructured":"Belichenko, P. V. et al. Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome. J Comp Neurol \n                           512, 453\u2013466, https:\/\/doi.org\/10.1002\/cne.21895 (2009).","journal-title":"J Comp Neurol"},{"key":"17201_CR121","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 \n                           480, 281\u2013298 (2004).","journal-title":"J Comp Neurol"},{"key":"17201_CR122","doi-asserted-by":"crossref","unstructured":"Rossi, C. et al. Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci, 1850\u20131856 (2006).","DOI":"10.1111\/j.1460-9568.2006.05059.x"},{"key":"17201_CR123","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.tins.2008.12.004","volume":"32","author":"A Sale","year":"2009","unstructured":"Sale, A., Berardi, N. & Maffei, L. Enrich the environment to empower the brain. Trends Neurosci \n                           32, 233\u2013239 (2009).","journal-title":"Trends Neurosci"},{"key":"17201_CR124","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 \n                           5, 29, https:\/\/doi.org\/10.3389\/fncel.2011.00029 (2011).","journal-title":"Front Cell Neurosci"},{"key":"17201_CR125","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.neuroscience.2012.06.007","volume":"219","author":"ML Mustroph","year":"2012","unstructured":"Mustroph, M. L. et al. Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL\/6\u2009J mice. Neuroscience \n                           219, 62\u201371 (2012).","journal-title":"Neuroscience"},{"key":"17201_CR126","doi-asserted-by":"publisher","first-page":"330","DOI":"10.3389\/fnbeh.2015.00330","volume":"9","author":"S Catuara-Solarz","year":"2015","unstructured":"Catuara-Solarz, S. et al. Principal Component Analysis of the Effects of Environmental Enrichment and (-)-epigallocatechin-3-gallate on Age-Associated Learning Deficits in a Mouse Model of Down Syndrome. Front Behav Neurosci \n                           9, 330 (2015).","journal-title":"Front Behav Neurosci"},{"key":"17201_CR127","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/S1474-4422(16)30034-5","volume":"15","author":"R de la Torre","year":"2016","unstructured":"de la Torre, R. et al. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down\u2019s syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol \n                           15, 801\u2013810, https:\/\/doi.org\/10.1016\/S1474-4422(16)30034-5 (2016).","journal-title":"Lancet Neurol"},{"key":"17201_CR128","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1111\/jir.12275","volume":"60","author":"SD Ringenbach","year":"2016","unstructured":"Ringenbach, S. D. et al. The effects of assisted cycling therapy (ACT) and voluntary cycling on reaction time and measures of executive function in adolescents with Down syndrome. J Intellect Disabil Res \n                           60, 1073\u20131085 (2016).","journal-title":"J Intellect Disabil Res"},{"key":"17201_CR129","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/jir.12258","volume":"60","author":"CC Chen","year":"2016","unstructured":"Chen, C. C. & Ringenbach, S. D. Dose-response relationship between intensity of exercise and cognitive performance in individuals with Down syndrome: a preliminary study. J Intellect Disabil Res \n                           60, 606\u2013614 (2016).","journal-title":"J Intellect Disabil Res"},{"key":"17201_CR130","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.ridd.2015.08.003","volume":"45-46","author":"SD Holzapfel","year":"2015","unstructured":"Holzapfel, S. D. et al. Improvements in manual dexterity relate to improvements in cognitive planning after assisted cycling therapy (ACT) in adolescents with down syndrome. Res Dev Disabil \n                           45-46, 261\u2013270 (2015).","journal-title":"Res Dev Disabil"},{"key":"17201_CR131","doi-asserted-by":"publisher","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. Behav Brain Res \n                           139, 47\u201357 (2003).","journal-title":"Behav Brain Res"},{"key":"17201_CR132","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1002\/cne.23663","volume":"523","author":"MJ Alldred","year":"2015","unstructured":"Alldred, M. J., Lee, S. H., Petkova, E. & Ginsberg, S. D. Expression profile analysis of vulnerable CA1 pyramidal neurons in young-Middle-Aged Ts65Dn mice. J Comp Neurol \n                           523, 61\u201374 (2015).","journal-title":"J Comp Neurol"},{"key":"17201_CR133","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1007\/s00429-014-0839-0","volume":"220","author":"MJ Alldred","year":"2015","unstructured":"Alldred, M. J., Lee, S. H., Petkova, E. & Ginsberg, S. D. Expression profile analysis of hippocampal CA1 pyramidal neurons in aged Ts65Dn mice, a model of Down syndrome (DS) and Alzheimer\u2019s disease (AD). Brain Struct Funct \n                           220, 2983\u20132996 (2015).","journal-title":"Brain Struct Funct"},{"key":"17201_CR134","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. Mol Cell Neurosci \n                           45, 226\u2013233, https:\/\/doi.org\/10.1016\/j.mcn.2010.06.013 (2010).","journal-title":"Mol Cell Neurosci"},{"key":"17201_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 \n                           74, 204\u2013218 (2015).","journal-title":"Neurobiology of Disease"},{"key":"17201_CR136","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. Journal of Neuroscience \n                           30, 8769\u20138779 (2010).","journal-title":"Journal of Neuroscience"},{"key":"17201_CR137","doi-asserted-by":"publisher","DOI":"10.1038\/srep45561","volume":"7","author":"SF Kazim","year":"2017","unstructured":"Kazim, S. F., Blanchard, J., Bianchi, R. & Iqbal, K. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer\u2019s-like memory deficits in the Ts65Dn mouse model of Down syndrome. Scientific reports \n                           7, 45561 (2017).","journal-title":"Scientific reports"},{"key":"17201_CR138","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.neuroscience.2009.08.054","volume":"164","author":"J Bakos","year":"2009","unstructured":"Bakos, J. et al. Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner. Neuroscience \n                           164, 788\u2013797 (2009).","journal-title":"Neuroscience"},{"key":"17201_CR139","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0169-328X(99)00137-0","volume":"71","author":"NC Berchtold","year":"1999","unstructured":"Berchtold, N. C., Oliff, H. S., Isackson, P. & Cotman, C. W. Hippocampal BDNF mRNA shows a diurnal regulation, primarily in the exon III transcript. Brain Res Mol Brain Res \n                           71, 11\u201322 (1999).","journal-title":"Brain Res Mol Brain Res"},{"key":"17201_CR140","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1037\/0735-7044.112.4.1012","volume":"112","author":"JP Kesslak","year":"1998","unstructured":"Kesslak, J. P., So, V., Choi, J., Cotman, C. W. & Gomez-Pinilla, F. Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: a mechanism to facilitate encoding and circuit maintenance? Behav Neurosci \n                           112, 1012\u20131019 (1998).","journal-title":"Behav Neurosci"},{"key":"17201_CR141","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/75698","volume":"3","author":"J Hall","year":"2000","unstructured":"Hall, J., Thomas, K. L. & Everitt, B. J. Rapid and selective induction of BDNF expression in the hippocampus during contextual learning. Nat Neurosci \n                           3, 533\u2013535 (2000).","journal-title":"Nat Neurosci"},{"key":"17201_CR142","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/0304-3940(92)90494-R","volume":"138","author":"T Falkenberg","year":"1992","unstructured":"Falkenberg, T. et al. Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Neurosci Lett \n                           138, 153\u2013156 (1992).","journal-title":"Neurosci Lett"},{"key":"17201_CR143","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 \n                           46, 297\u2013303 (2012).","journal-title":"Molecular neurobiology"},{"key":"17201_CR144","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nrn2738","volume":"10","author":"L Minichiello","year":"2009","unstructured":"Minichiello, L. TrkB signalling pathways in LTP and learning. Nature reviews. Neuroscience \n                           10, 850\u2013860, https:\/\/doi.org\/10.1038\/nrn2738 (2009).","journal-title":"Nature reviews. Neuroscience"},{"key":"17201_CR145","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.neuropharm.2013.05.043","volume":"76","author":"E Edelmann","year":"2014","unstructured":"Edelmann, E., Lebmann, V. & Brigadski, T. Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity. Neuropharmacology \n                           76, 610\u2013627 (2014).","journal-title":"Neuropharmacology"},{"key":"17201_CR146","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature19766","volume":"538","author":"SC Harward","year":"2016","unstructured":"Harward, S. C. et al. Autocrine BDNF-TrkB signalling within a single dendritic spine. Nature \n                           538, 99\u2013103 (2016).","journal-title":"Nature"},{"key":"17201_CR147","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.neuropharm.2013.04.005","volume":"76","author":"G Leal","year":"2014","unstructured":"Leal, G., Comprido, D. & Duarte, C. B. BDNF-induced local protein synthesis and synaptic plasticity. Neuropharmacology \n                           76, 639\u2013656 (2014).","journal-title":"Neuropharmacology"},{"key":"17201_CR148","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.nbd.2015.02.022","volume":"77","author":"RL Nosheny","year":"2015","unstructured":"Nosheny, R. L. et al. Increased cortical synaptic activation of TrkB and downstream signaling markers in a mouse model of Down Syndrome. Neurobiol Dis \n                           77, 173\u2013190 (2015).","journal-title":"Neurobiol Dis"},{"key":"17201_CR149","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1152\/japplphysiol.01361.2011","volume":"112","author":"RA Johnson","year":"2012","unstructured":"Johnson, R. A. et al. 7,8-dihydroxyflavone exhibits therapeutic efficacy in a mouse model of Rett syndrome. Journal of applied physiology \n                           112, 704\u2013710 (2012).","journal-title":"Journal of applied physiology"},{"key":"17201_CR150","doi-asserted-by":"publisher","DOI":"10.1038\/srep34339","volume":"6","author":"J He","year":"2016","unstructured":"He, J. et al. Neuroprotective Effects of 7,8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+ -treated Monkeys. Scientific reports \n                           6, 34339 (2016).","journal-title":"Scientific reports"},{"key":"17201_CR151","doi-asserted-by":"publisher","unstructured":"Zhang, J. C. et al. Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation. Int J Neuropsychopharmacol \n                           18, https:\/\/doi.org\/10.1093\/ijnp\/pyu077 (2014).","DOI":"10.1093\/ijnp\/pyu077"},{"key":"17201_CR152","doi-asserted-by":"publisher","first-page":"e91453","DOI":"10.1371\/journal.pone.0091453","volume":"9","author":"NA Castello","year":"2014","unstructured":"Castello, N. A. et al. 7,8-Dihydroxyflavone, a small molecule TrkB agonist, improves spatial memory and increases thin spine density in a mouse model of Alzheimer disease-like neuronal loss. PLoS One \n                           9, e91453 (2014).","journal-title":"PLoS One"},{"key":"17201_CR153","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1242\/dev.00203","volume":"130","author":"G Kempermann","year":"2003","unstructured":"Kempermann, G., Gast, D., Kronenberg, G., Yamaguchi, M. & Gage, F. H. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development \n                           130, 391\u2013399 (2003).","journal-title":"Development"},{"key":"17201_CR154","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/S0896-6273(00)80409-2","volume":"19","author":"EB Ziff","year":"1997","unstructured":"Ziff, E. B. Enlightening the postsynaptic density. Neuron \n                           19, 1163\u20131174 (1997).","journal-title":"Neuron"},{"key":"17201_CR155","doi-asserted-by":"publisher","first-page":"a005678","DOI":"10.1101\/cshperspect.a005678","volume":"3","author":"M Sheng","year":"2011","unstructured":"Sheng, M. & Kim, E. The Postsynaptic Organization of Synapses. Cold Spring Harb Perspect Biol \n                           3, a005678 (2011).","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"17201_CR156","doi-asserted-by":"crossref","unstructured":"Pozzi, D. et al. REST\/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability. EMBO J \n                           32, 2994\u20133007, emboj2013231 [pii] 10.1038\/emboj.2013.231 (2013).","DOI":"10.1038\/emboj.2013.231"},{"key":"17201_CR157","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034","volume":"3","author":"J Vandesompele","year":"2002","unstructured":"Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol \n                           3, RESEARCH0034 (2002).","journal-title":"Genome Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17201-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17201-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17201-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T14:52:53Z","timestamp":1671807173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17201-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,4]]},"references-count":157,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["17201"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-17201-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,4]]},"assertion":[{"value":"14 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16825"}}