Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture.
Developmental neuroscience
Model organism
Transcriptomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
17 Feb 2023
17 Feb 2023
Historique:
received:
18
10
2022
revised:
22
12
2022
accepted:
24
01
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
24
2
2023
Statut:
epublish
Résumé
The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21.
Identifiants
pubmed: 36818290
doi: 10.1016/j.isci.2023.106073
pii: S2589-0042(23)00150-5
pmc: PMC9929862
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106073Subventions
Organisme : Medical Research Council
ID : MR/V034758/1
Pays : United Kingdom
Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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