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Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome

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...

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Autores principales: Moreno, David G., Utagawa, Emma C., Arva, Nicoleta C., Schafernak, Kristian T., Mufson, Elliott J., Perez, Sylvia E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347520/
https://www.ncbi.nlm.nih.gov/pubmed/34362198
http://dx.doi.org/10.3390/jcm10153414
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author Moreno, David G.
Utagawa, Emma C.
Arva, Nicoleta C.
Schafernak, Kristian T.
Mufson, Elliott J.
Perez, Sylvia E.
author_facet Moreno, David G.
Utagawa, Emma C.
Arva, Nicoleta C.
Schafernak, Kristian T.
Mufson, Elliott J.
Perez, Sylvia E.
author_sort Moreno, David G.
collection PubMed
description 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’-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 (Aβ) 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/Aβ-ir diffuse-like plaques were seen in DS and NTD. By contrast, no Aβ(1–42) 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.
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spelling pubmed-83475202021-08-08 Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome Moreno, David G. Utagawa, Emma C. Arva, Nicoleta C. Schafernak, Kristian T. Mufson, Elliott J. Perez, Sylvia E. J Clin Med Article 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’-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 (Aβ) 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/Aβ-ir diffuse-like plaques were seen in DS and NTD. By contrast, no Aβ(1–42) 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. MDPI 2021-07-31 /pmc/articles/PMC8347520/ /pubmed/34362198 http://dx.doi.org/10.3390/jcm10153414 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moreno, David G.
Utagawa, Emma C.
Arva, Nicoleta C.
Schafernak, Kristian T.
Mufson, Elliott J.
Perez, Sylvia E.
Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome
title Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome
title_full Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome
title_fullStr Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome
title_full_unstemmed Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome
title_short Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome
title_sort postnatal cytoarchitecture and neurochemical hippocampal dysfunction in down syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347520/
https://www.ncbi.nlm.nih.gov/pubmed/34362198
http://dx.doi.org/10.3390/jcm10153414
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