{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T09:13:52Z","timestamp":1788081232408,"version":"build-2784847793"},"reference-count":86,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Generali"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Down syndrome (DS) is characterized by severe neurodevelopmental alterations that ultimately lead to the typical hallmark of DS: intellectual disability. In the DS brain, since the prenatal life stages, the number of astrocytes is disproportional compared to the healthy brain. This increase is due to a shift from neuron to astrocyte differentiation during brain development. Astrocytes are involved in numerous functions during brain development, including balancing pro-neurogenic and pro-gliogenic stimuli, sustaining synapse formation, regulating excitatory\/inhibitory signal equilibrium, and supporting the maintenance and integration of functional neural circuits. The enhanced number of astrocytes in the brain of DS individuals leads to detrimental consequences for brain development. This review summarizes the mechanisms underlying astrocytic dysfunction in DS, and particularly the dysregulation of key signaling pathways, which promote astrogliogenesis at the expense of neurogenesis. It further examines the implications of astrocytic alterations on dendritic branching, spinogenesis and synaptogenesis, and the impact of the abnormal astrocytic number in neural excitability and in the maintenance of the inhibitory\/excitatory balance. Identifying deregulated pathways and the consequences of astrocytic alterations in early DS brain development may help in identifying new therapeutic targets, with the ultimate aim of ameliorating the cognitive disability that affects individuals with DS.<\/jats:p>","DOI":"10.3390\/cells13242037","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T08:40:10Z","timestamp":1733820010000},"page":"2037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Astrocytic Alterations and Dysfunction in Down Syndrome: Focus on Neurogenesis, Synaptogenesis, and Neural Circuits Formation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7944-5368","authenticated-orcid":false,"given":"Beatrice","family":"Uguagliati","sequence":"first","affiliation":[{"name":"Laboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-5827","authenticated-orcid":false,"given":"Mariagrazia","family":"Grilli","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/ddrr.1127","article-title":"Aging and intellectual disability: Insights from mouse models of down syndrome","volume":"18","author":"Ruparelia","year":"2013","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/nrn3314","article-title":"Down syndrome: The brain in trisomic mode","volume":"13","author":"Dierssen","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e3186","DOI":"10.1002\/brb3.3186","article-title":"Correlating MRI-based brain volumetry and cognitive assessment in people with Down syndrome","volume":"13","author":"Hamadelseed","year":"2023","journal-title":"Brain Behav."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1002\/pd.6436","article-title":"Biometric magnetic resonance imaging analysis of fetal brain development in down syndrome","volume":"43","author":"Kitano","year":"2023","journal-title":"Prenat. Diagn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1093\/cercor\/bhz094","article-title":"Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome","volume":"30","author":"Tarui","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102139","DOI":"10.1016\/j.nicl.2019.102139","article-title":"Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment","volume":"25","author":"Patkee","year":"2020","journal-title":"NeuroImage Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/bpa.12663","article-title":"Subicular hypotrophy in fetuses with Down syndrome and in the Ts65Dn model of Down syndrome","volume":"29","author":"Stagni","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1750-3639.2007.00113.x","article-title":"RESEARCH ARTICLE: Neurogenesis Impairment and Increased Cell Death Reduce Total Neuron Number in the Hippocampal Region of Fetuses with Down Syndrome","volume":"18","author":"Guidi","year":"2008","journal-title":"Brain Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1750-3639.2010.00459.x","article-title":"Widespread Proliferation Impairment and Hypocellularity in the Cerebellum of Fetuses with Down Syndrome","volume":"21","author":"Guidi","year":"2011","journal-title":"Brain Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s40478-020-01015-3","article-title":"Assessment of radial glia in the frontal lobe of fetuses with Down syndrome","volume":"8","author":"Baburamani","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1159\/000236899","article-title":"A Critical Period in Cortical Interneuron Neurogenesis in Down Syndrome Revealed by Human Neural Progenitor Cells","volume":"31","author":"Bhattacharyya","year":"2009","journal-title":"Dev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/dneu.22953","article-title":"Cellularity Defects Are Not Ubiquitous in the Brains of Fetuses with Down Syndrome","volume":"84","author":"Emili","year":"2024","journal-title":"Dev. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.ijdevneu.2013.09.011","article-title":"Non-neuronal cell responses differ between normal and Down syndrome developing brains","volume":"31","author":"Kanaumi","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_14","first-page":"109","article-title":"Astroglia disturbances during development of the central nervous system in fetuses with Down\u2019s syndrome","volume":"49","author":"Zdaniuk","year":"2011","journal-title":"Folia Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105870","DOI":"10.1016\/j.clineuro.2020.105870","article-title":"Neuroanatomical alterations in higher-order thalamic nuclei of fetuses with Down syndrome","volume":"194","author":"Stagni","year":"2020","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1465","DOI":"10.1542\/peds.2006-3448","article-title":"Fetal Down Syndrome Brains Exhibit Aberrant Levels of Neurotransmitters Critical for Normal Brain Development","volume":"120","author":"Whittle","year":"2007","journal-title":"Pediatrics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101874","DOI":"10.1016\/j.nicl.2019.101874","article-title":"Structural magnetic resonance imaging demonstrates abnormal cortical thickness in Down syndrome: Newborns to young adults","volume":"23","author":"Levman","year":"2019","journal-title":"NeuroImage Clin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/hmg\/9.2.195","article-title":"Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse","volume":"9","author":"Baxter","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1046\/j.1365-2788.2002.00362.x","article-title":"Quantitative comparison of radial cell columns in children with Down\u2019s syndrome and controls","volume":"46","author":"Buxhoeveden","year":"2002","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1017\/S1355617718000206","article-title":"Pediatric Brain Development in Down Syndrome: A Field in Its Infancy","volume":"24","author":"Hamner","year":"2018","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1006\/exnr.1993.1052","article-title":"Developmental Changes of S-100 Protein and Glial Fibrillary Acidic Protein in the Brain in Down Syndrome","volume":"120","author":"Mito","year":"1993","journal-title":"Exp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0006-8993(81)90314-0","article-title":"Abnormal neuronal development in the visual cortex of the human fetus and infant with down\u2019s syndrome. A quantitative and qualitative Golgi study","volume":"225","author":"Takashima","year":"1981","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2788.1994.tb00394.x","article-title":"Dendritic and histochemical development and ageing in patients with Down\u2019s syndrome","volume":"38","author":"Takashima","year":"1994","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/ana.410200413","article-title":"Dendritic Atrophy in Chidren with Down\u2019s Syndrome","volume":"20","author":"Becker","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/cne.901670105","article-title":"PyramidalCell Abnormalities in the Motor Cortex of a Child with Down\u2019s Syndrome. A Golgi Study","volume":"167","year":"1976","journal-title":"J. Comp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1128\/MCB.02435-06","article-title":"Potentiation of Astrogliogenesis by STAT3-Mediated Activation of Bone Morphogenetic Protein-Smad Signaling in Neural Stem Cells","volume":"27","author":"Fukuda","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1002\/glia.23630","article-title":"Astrocyte-to-astrocyte contact and a positive feedback loop of growth factor signaling regulate astrocyte maturation","volume":"67","author":"Li","year":"2019","journal-title":"Glia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1002\/glia.23498","article-title":"Inhibition of astrocyte FAK\u2013JNK signaling promotes subventricular zone neurogenesis through CNTF","volume":"66","author":"Jia","year":"2018","journal-title":"Glia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1634\/stemcells.2008-0222","article-title":"Ciliary Neurotrophic Factor-Mediated Signaling Regulates Neuronal Versus Glial Differentiation of Retinal Stem Cells\/Progenitors by Concentration-Dependent Recruitment of Mitogen-Activated Protein Kinase and Janus Kinase-Signal Transducer and Activator of Transcription Pathways in Conjunction with Notch Signaling","volume":"26","author":"Bhattacharya","year":"2008","journal-title":"Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1093\/cercor\/bhz031","article-title":"Foxg1 Antagonizes Neocortical Stem Cell Progression to Astrogenesis","volume":"29","author":"Falcone","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature10959","article-title":"Local generation of glia is a major astrocyte source in postnatal cortex","volume":"484","author":"Ge","year":"2012","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.neuron.2017.09.056","article-title":"Cell Biology of Astrocyte-Synapse Interactions","volume":"96","author":"Allen","year":"2017","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/1873-3468.13502","article-title":"Wnt\/beta-catenin signaling in brain development and mental disorders: Keeping TCF7L2 in mind","volume":"593","author":"Bem","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/s41593-022-01150-1","article-title":"Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders","volume":"25","author":"Caldwell","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1083\/jcb.201802057","article-title":"Thrombospondin receptor alpha2delta-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1","volume":"217","author":"Risher","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e99529","DOI":"10.15252\/embj.201899529","article-title":"Pentraxin 3 regulates synaptic function by inducing AMPA receptor clustering via ECM remodeling and beta1-integrin","volume":"38","author":"Fossati","year":"2019","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/nature11059","article-title":"Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors","volume":"486","author":"Allen","year":"2012","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1002\/glia.22713","article-title":"Astrocyte transforming growth factor beta 1 promotes inhibitory synapse formation via CaM kinase II signaling","volume":"62","author":"Diniz","year":"2014","journal-title":"Glia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41586-020-2926-0","article-title":"Chemico-genetic discovery of astrocytic control of inhibition in vivo","volume":"588","author":"Takano","year":"2020","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12524","DOI":"10.1073\/pnas.0903328106","article-title":"Glial ephrin-A3 regulates hippocampal dendritic spine morphology and glutamate transport","volume":"106","author":"Carmona","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1038\/s41467-020-18024-4","article-title":"Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development","volume":"11","author":"Oliveira","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1523\/JNEUROSCI.3965-04.2005","article-title":"Properties of Synaptically Evoked Astrocyte Calcium Signal Reveal Synaptic Information Processing by Astrocytes","volume":"25","author":"Perea","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nature24638","article-title":"Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis","volume":"551","author":"Stogsdill","year":"2017","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature12776","article-title":"Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways","volume":"504","author":"Chung","year":"2013","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1101\/lm.2.1.26","article-title":"Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice","volume":"2","author":"Gerlai","year":"1995","journal-title":"Learn. Mem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Manninen, T., Saudargiene, A., and Linne, M.-L. (2020). Astrocyte-mediated spike-timing-dependent long-term depression modulates synaptic properties in the developing cortex. PLoS Comput. Biol., 16.","DOI":"10.1371\/journal.pcbi.1008360"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7611","DOI":"10.1073\/pnas.86.19.7611","article-title":"Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease","volume":"86","author":"Griffin","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/emmm.201302848","article-title":"Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21","volume":"6","author":"Hibaoui","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.expneurol.2004.11.024","article-title":"Development of interlaminar astroglial processes in the cerebral cortex of control and Down\u2019s syndrome human cases","volume":"193","author":"Colombo","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bally, B.P., and Murai, K.K. (2021). Astrocytes in Down Syndrome Across the Lifespan. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.702685"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.freeradbiomed.2017.07.026","article-title":"Neurogenesis impairment: An early developmental defect in Down syndrome","volume":"114","author":"Stagni","year":"2018","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e16220","DOI":"10.7554\/eLife.16220","article-title":"Trisomy 21 consistently activates the interferon response","volume":"5","author":"Sullivan","year":"2016","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1073\/pnas.95.11.6256","article-title":"Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities","volume":"95","author":"Sago","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.15252\/embr.201540374","article-title":"DYRK 1A overexpression enhances STAT activity and astrogliogenesis in a Down syndrome mouse model","volume":"16","author":"Kurabayashi","year":"2015","journal-title":"Embo Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/00207454.2019.1580280","article-title":"Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje down syndrome mouse model","volume":"129","author":"Lee","year":"2019","journal-title":"Int. J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.nbd.2012.01.007","article-title":"DYRK1A: A master regulatory protein controlling brain growth","volume":"46","author":"Guedj","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S0140-6736(02)07497-4","article-title":"Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down\u2019s syndrome: A gene expression study","volume":"359","author":"Bahn","year":"2002","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ygeno.2007.08.005","article-title":"Gene expression profiling in the adult Down syndrome brain","volume":"90","author":"Lockstone","year":"2007","journal-title":"Genomics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1007\/s12031-019-01275-2","article-title":"Expression Profiling of Notch Signalling Pathway and Gamma-Secretase Activity in the Brain of Ts1Cje Mouse Model of Down Syndrome","volume":"67","author":"Yusof","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1146\/annurev.cellbio.20.010403.113126","article-title":"The wnt signaling pathway in development and disease","volume":"20","author":"Logan","year":"2004","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Martinez, J.L., Piciw, J.G., Crockett, M., Sorci, I.A., Makwana, N., Sirois, C.L., Giffin-Rao, Y., and Bhattacharyya, A. (2024). Transcriptional consequences of trisomy 21 on neural induction. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1341141"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/glia.23608","article-title":"WNT signaling represses astrogliogenesis via Ngn2-dependent direct suppression of astrocyte gene expression","volume":"67","author":"Sun","year":"2019","journal-title":"Glia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1097\/00005072-199409000-00011","article-title":"Development of the Superior Temporal Neocortex Is Anomalous in Trisomy 21","volume":"53","author":"Golden","year":"1994","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Farizatto, K.L., and Baldwin, K.T. (2023). Astrocyte-synapse interactions during brain development. Curr. Opin. Neurobiol., 80.","DOI":"10.1016\/j.conb.2023.102704"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.freeradbiomed.2017.09.025","article-title":"Dendritic spine pathology and thrombospondin-1 deficits in Down syndrome","volume":"114","author":"Torres","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Garcia, O., Torres, M., Helguera, P., Coskun, P., and Busciglio, J. (2010). A role for thrombospondin-1 deficits in astrocyte-mediated spine and synaptic pathology in Down\u2019s syndrome. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014200"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18103\/mra.v10i10.3168","article-title":"Thrombospondin-1 (TSP-1) and Neuronal Plasticity: Implications in Down Syndrome","volume":"10","author":"Garcia","year":"2022","journal-title":"Med. Res. Arch."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.bbadis.2014.04.007","article-title":"Neuropathological role of PI3K\/Akt\/mTOR axis in Down syndrome brain","volume":"1842","author":"Perluigi","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9445","DOI":"10.1523\/JNEUROSCI.0011-11.2011","article-title":"An increase in basal BDNF provokes hyperactivation of the Akt-mammalian target of rapamycin pathway and deregulation of local dendritic translation in a mouse model of Down\u2019s syndrome","volume":"31","author":"Montesinos","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.1007\/s12035-017-0818-6","article-title":"Down Syndrome iPSC-Derived Astrocytes Impair Neuronal Synaptogenesis and the mTOR Pathway In Vitro","volume":"55","author":"Araujo","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/ng1095-177","article-title":"A mouse model for Down syndrome exhibits learning and behaviour deficits","volume":"11","author":"Reeves","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1901152","DOI":"10.1002\/advs.201901152","article-title":"IGFBP2 Plays an Essential Role in Cognitive Development during Early Life","volume":"6","author":"Khan","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/hmg\/ddaa003","article-title":"Human iPSC-derived Down syndrome astrocytes display genome-wide perturbations in gene expression, an altered adhesion profile, and increased cellular dynamics","volume":"29","author":"Farmer","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1080\/15592294.2016.1192736","article-title":"Epigenetic dysregulation in the developing Down syndrome cortex","volume":"11","author":"Dittrich","year":"2016","journal-title":"Epigenetics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1523\/JNEUROSCI.23-12-05096.2003","article-title":"Gamma-protocadherins are targeted to subsets of synapses and intracellular organelles in neurons","volume":"23","author":"Phillips","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"694","DOI":"10.2174\/1567205011666140812115423","article-title":"Metabotropic glutamate receptor 5 in Down\u2019s syndrome hippocampus during development: Increased expression in astrocytes","volume":"11","author":"Iyer","year":"2014","journal-title":"Curr. Alzheimer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.celrep.2018.06.033","article-title":"Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model","volume":"24","author":"Mizuno","year":"2018","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jnr.10630","article-title":"Altered astrocyte calcium homeostasis and proliferation in theTs65Dn mouse, a model of Down syndrome","volume":"73","author":"Bambrick","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/0361-9230(86)90076-6","article-title":"Genetic basis for a mouse model of down syndrome","volume":"16","author":"Reeves","year":"1986","journal-title":"Brain Res. Bull."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.freeradbiomed.2017.10.002","article-title":"GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrom","volume":"114","author":"Delabar","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrn920","article-title":"Excitatory actions of gaba during development: The nature of the nurture","volume":"3","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5906","DOI":"10.1093\/cercor\/bhac470","article-title":"Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development","volume":"33","author":"Kurki","year":"2023","journal-title":"Cereb. Cortex"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41467-020-14865-1","article-title":"Author Correction: Role of astroglia in Down\u2019s syndrome revealed by patient-derived human-induced pluripotent stem cells","volume":"11","author":"Chen","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.yebeh.2015.10.004","article-title":"Cerebal overinhibition could be the basis for the high prevalence of epilepsy in persons with Down syndrome","volume":"53","author":"Araujo","year":"2015","journal-title":"Epilepsy Behav."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Xu, S.Y., Lu, F.M., Wang, M.Y., Hu, Z.S., Zhang, J., Chen, Z.Y., and Yuan, Z. (2020). Altered Functional Connectivity in the Motor and Prefrontal Cortex for Children with Down\u2019s Syndrome: An fNIRS Study. Front. Hum. Neurosci., 14.","DOI":"10.3389\/fnhum.2020.00006"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Garcia, O., and Flores-Aguilar, L. (2022). Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer\u2019s disease. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.987212"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/24\/2037\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:51:22Z","timestamp":1760115082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/24\/2037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,10]]},"references-count":86,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["cells13242037"],"URL":"https:\/\/doi.org\/10.3390\/cells13242037","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,10]]}}}