{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:23:50Z","timestamp":1780503830522,"version":"3.54.1"},"reference-count":89,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Investigaci\u00f3n Valdecilla, Santander, Spain","award":["IDIVAL; NVAL 19\/23"],"award-info":[{"award-number":["IDIVAL; NVAL 19\/23"]}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas\u201d  Spain","award":["(CIBERNED; CB06\/05\/0037)"],"award-info":[{"award-number":["(CIBERNED; CB06\/05\/0037)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22031259","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:20:26Z","timestamp":1611750026000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nuclear Reorganization in Hippocampal Granule Cell Neurons from a Mouse Model of Down Syndrome: Changes in Chromatin Configuration, Nucleoli and Cajal Bodies"],"prefix":"10.3390","volume":"22","author":[{"given":"Alba","family":"Puente-Bedia","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda T.","family":"Berciano","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, \u201cRed sobre Enfermedades Neurodegenerativas (CIBERNED)\u201d and University of Cantabria-IDIVAL, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0802-7975","authenticated-orcid":false,"given":"Olga","family":"Tapia","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), \u201cRed sobre Enfermedades Neurodegenerativas (CIBERNED)\u201d and Universidad Europea del Atl\u00e1ntico, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-1156","authenticated-orcid":false,"given":"Carmen","family":"Mart\u00ednez-Cu\u00e9","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Lafarga","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, \u201cRed sobre Enfermedades Neurodegenerativas (CIBERNED)\u201d and University of Cantabria-IDIVAL, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noem\u00ed","family":"Rueda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1542\/peds.2009-0745","article-title":"The Congenital Anomaly Multistate Prevalence and Survival (CAMPS) Collaborative. 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