{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:41:37Z","timestamp":1787611297711,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P01AG014449"],"award-info":[{"award-number":["P01AG014449"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["CA2018010"],"award-info":[{"award-number":["CA2018010"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014813","name":"Arizona Alzheimer\u2019s Consortium","doi-asserted-by":"publisher","award":["P30AG010161"],"award-info":[{"award-number":["P30AG010161"]}],"id":[{"id":"10.13039\/100014813","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Although the prenatal hippocampus displays deficits in cellular proliferation\/migration and volume, which are later associated with memory deficits, little is known about the effects of trisomy 21 on postnatal hippocampal cellular development in Down syndrome (DS). We examined postnatal hippocampal neuronal profiles from autopsies of DS and neurotypical (NTD) neonates born at 38-weeks\u2019-gestation up to children 3 years of age using antibodies against non-phosphorylated (SMI-32) and phosphorylated (SMI-34) neurofilament, calbindin D-28k (Calb), calretinin (Calr), parvalbumin (Parv), doublecortin (DCX) and Ki-67, as well as amyloid precursor protein (APP), amyloid beta (A\u03b2) and phosphorylated tau (p-tau). Although the distribution of SMI-32-immunoreactive (-ir) hippocampal neurons was similar at all ages in both groups, pyramidal cell apical and basal dendrites were intensely stained in NTD cases. A greater reduction in the number of DCX-ir cells was observed in the hippocampal granule cell layer in DS. Although the distribution of Calb-ir neurons was similar between the youngest and oldest NTD and DS cases, Parv-ir was not detected. Conversely, Calr-ir cells and fibers were observed at all ages in DS, while NTD cases displayed mainly Calr-ir fibers. Hippocampal APP\/A\u03b2-ir diffuse-like plaques were seen in DS and NTD. By contrast, no A\u03b21\u201342 or p-tau profiles were observed. These findings suggest that deficits in hippocampal neurogenesis and pyramidal cell maturation and increased Calr immunoreactivity during early postnatal life contribute to cognitive impairment in DS.<\/jats:p>","DOI":"10.3390\/jcm10153414","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"3414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome"],"prefix":"10.3390","volume":"10","author":[{"given":"David G.","family":"Moreno","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C.","family":"Utagawa","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoleta C.","family":"Arva","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian T.","family":"Schafernak","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott J.","family":"Mufson","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1542\/peds.2011-1605","article-title":"Health supervision for children with Down syndrome","volume":"128","author":"Bull","year":"2011","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.tins.2011.11.001","article-title":"Trisomy 21 and early brain development","volume":"35","author":"Haydar","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/0361-9230(86)90074-2","article-title":"The neurobiologic consequences of Down syndrome","volume":"16","author":"Coyle","year":"1986","journal-title":"Brain Res. 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