Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies

Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells...

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Authors: Puente Bedia, Alba, Berciano Blanco, María Teresa, Tapia Martínez, Olga, Martínez-Cué, Carmen|||0000-0002-2137-1156, Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152, Rueda Revilla, Noemí
Format: article
Publication Date:2021
Country:España
Institution:Universidad de Cantabria (UC)
Repository:UCrea Repositorio Abierto de la Universidad de Cantabria
Language:English
OAI Identifier:oai:repositorio.unican.es:10902/21130
Online Access:http://hdl.handle.net/10902/21130
Access Level:Open access
Keyword:Ts65Dn
Hippocampus
Down syndrome
Nucleolus
Cajal body
Chromatin
NORs
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spelling Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodiesPuente Bedia, AlbaBerciano Blanco, María TeresaTapia Martínez, OlgaMartínez-Cué, Carmen|||0000-0002-2137-1156Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152Rueda Revilla, NoemíTs65DnHippocampusDown syndromeNucleolusCajal bodyChromatinNORsDown syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed that the additional gene dose in trisomic cells induces modifications in nuclear compartments and on the chromatin landscape, which could contribute to some DS phenotypes. The Ts65Dn (TS) mouse model of DS carries a triplication of 92 genes orthologous to those found in Hsa21, and shares many phenotypes with DS individuals, including cognitive and neuromorphological alterations. Considering its essential role in hippocampal memory formation, we investigated whether the triplication of this set of Hsa21 orthologous genes in TS mice modifies the nuclear architecture of their GCs. Our results show that the TS mouse presents alterations in the nuclear architecture of its GCs, affecting nuclear compartments involved in transcription and pre-rRNA and pre-mRNA processing. In particular, the GCs of the TS mouse show alterations in the nucleolar fusion pattern and the molecular assembly of Cajal bodies (CBs). Furthermore, hippocampal GCs of TS mice present an epigenetic dysregulation of chromatin that results in an increased heterochromatinization and reduced global transcriptional activity. These nuclear alterations could play an important role in the neuromorphological and/or functional alterations of the hippocampal GCs implicated in the cognitive dysfunction characteristic of TS mice.MDPIUniversidad de Cantabria20212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/21130Int. J. Mol. Sci. 2021, 22(3), 1259reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/211302026-06-02T12:39:31Z
dc.title.none.fl_str_mv Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
title Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
spellingShingle Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
Puente Bedia, Alba
Ts65Dn
Hippocampus
Down syndrome
Nucleolus
Cajal body
Chromatin
NORs
title_short Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
title_full Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
title_fullStr Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
title_full_unstemmed Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
title_sort Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies
dc.creator.none.fl_str_mv Puente Bedia, Alba
Berciano Blanco, María Teresa
Tapia Martínez, Olga
Martínez-Cué, Carmen|||0000-0002-2137-1156
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Rueda Revilla, Noemí
author Puente Bedia, Alba
author_facet Puente Bedia, Alba
Berciano Blanco, María Teresa
Tapia Martínez, Olga
Martínez-Cué, Carmen|||0000-0002-2137-1156
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Rueda Revilla, Noemí
author_role author
author2 Berciano Blanco, María Teresa
Tapia Martínez, Olga
Martínez-Cué, Carmen|||0000-0002-2137-1156
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Rueda Revilla, Noemí
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Ts65Dn
Hippocampus
Down syndrome
Nucleolus
Cajal body
Chromatin
NORs
topic Ts65Dn
Hippocampus
Down syndrome
Nucleolus
Cajal body
Chromatin
NORs
description Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed that the additional gene dose in trisomic cells induces modifications in nuclear compartments and on the chromatin landscape, which could contribute to some DS phenotypes. The Ts65Dn (TS) mouse model of DS carries a triplication of 92 genes orthologous to those found in Hsa21, and shares many phenotypes with DS individuals, including cognitive and neuromorphological alterations. Considering its essential role in hippocampal memory formation, we investigated whether the triplication of this set of Hsa21 orthologous genes in TS mice modifies the nuclear architecture of their GCs. Our results show that the TS mouse presents alterations in the nuclear architecture of its GCs, affecting nuclear compartments involved in transcription and pre-rRNA and pre-mRNA processing. In particular, the GCs of the TS mouse show alterations in the nucleolar fusion pattern and the molecular assembly of Cajal bodies (CBs). Furthermore, hippocampal GCs of TS mice present an epigenetic dysregulation of chromatin that results in an increased heterochromatinization and reduced global transcriptional activity. These nuclear alterations could play an important role in the neuromorphological and/or functional alterations of the hippocampal GCs implicated in the cognitive dysfunction characteristic of TS mice.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10902/21130
url http://hdl.handle.net/10902/21130
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Int. J. Mol. Sci. 2021, 22(3), 1259
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403634513477632
score 15,300719

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