Your browser doesn't support javascript.
loading
Investigating brain alterations in the Dp1Tyb mouse model of Down syndrome.
Serrano, Maria Elisa; Kim, Eugene; Siow, Bernard; Ma, Da; Rojo, Loreto; Simmons, Camilla; Hayward, Darryl; Gibbins, Dorota; Singh, Nisha; Strydom, Andre; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Cash, Diana.
Afiliación
  • Serrano ME; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
  • Kim E; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
  • Siow B; The Francis Crick Institute, London, United Kingdom.
  • Ma D; Department of Internal Medicine Section of Gerontology and Geriatric Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
  • Rojo L; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
  • Simmons C; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
  • Hayward D; The Francis Crick Institute, London, United Kingdom.
  • Gibbins D; The Francis Crick Institute, London, United Kingdom.
  • Singh N; Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
  • Strydom A; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • Fisher EMC; UCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
  • Tybulewicz VLJ; The Francis Crick Institute, London, United Kingdom.
  • Cash D; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
Neurobiol Dis ; 188: 106336, 2023 Nov.
Article en En | MEDLINE | ID: mdl-38317803
ABSTRACT
Down syndrome (DS) is one of the most common birth defects and the most prevalent genetic form of intellectual disability. DS arises from trisomy of chromosome 21, but its molecular and pathological consequences are not fully understood. In this study, we compared Dp1Tyb mice, a DS model, against their wild-type (WT) littermates of both sexes to investigate the impact of DS-related genetic abnormalities on the brain phenotype. We performed in vivo whole brain magnetic resonance imaging (MRI) and hippocampal 1H magnetic resonance spectroscopy (MRS) on the animals at 3 months of age. Subsequently, ex vivo MRI scans and histological analyses were conducted post-mortem. Our findings unveiled the following neuroanatomical and biochemical alterations in the Dp1Tyb brains a smaller surface area and a rounder shape compared to WT brains, with DS males also presenting smaller global brain volume compared with the counterpart WT. Regional volumetric analysis revealed significant changes in 26 out of 72 examined brain regions, including the medial prefrontal cortex and dorsal hippocampus. These alterations were consistently observed in both in vivo and ex vivo imaging data. Additionally, high-resolution ex vivo imaging enabled us to investigate cerebellar layers and hippocampal sub-regions, revealing selective areas of decrease and remodelling in these structures. An analysis of hippocampal metabolites revealed an elevation in glutamine and the glutamine/glutamate ratio in the Dp1Tyb mice compared to controls, suggesting a possible imbalance in the excitation/inhibition ratio. This was accompanied by the decreased levels of taurine. Histological analysis revealed fewer neurons in the hippocampal CA3 and DG layers, along with an increase in astrocytes and microglia. These findings recapitulate multiple neuroanatomical and biochemical features associated with DS, enriching our understanding of the potential connection between chromosome 21 trisomy and the resultant phenotype.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Down Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Neurobiol Dis Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Down Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Neurobiol Dis Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos