title: Morphological alterations in the hippocampus of the Ts65Dn mouse model for Down Syndrome correlate with structural plasticity markers.
abstract: Down syndrome (DS) is the most common chromosomal aneuploidy. Although trisomy on chromosome 21 can display variable phenotypes, there is a common feature among all DS individuals: the presence of intellectual disability. This condition is partially attributed to abnormalities found in the hippocampus of individuals with DS and in the murine model for DS, Ts65Dn. To check if all hippocampal areas were equally affected in 4-5 month adult Ts65Dn mice, we analysed the morphology of dentate gyrus granule cells and cornu ammonis pyramidal neurons using Sholl method on Golgi-Cox impregnated neurons. Structural plasticity has been analysed using immunohistochemistry for plasticity molecules followed by densitometric analysis (Brain Derived Neurotrophic Factor (BDNF), Polysialylated form of the Neural Cell Adhesion Molecule (PSA-NCAM) and the Growth Associated Protein 43 (GAP43)). We observed an impairment in the dendritic arborisation of granule cells, but not in the pyramidal neurons in the Ts65Dn mice. When we analysed the expression of molecules related to structural plasticity in trisomic mouse hippocampus, we observed a reduction in the expression of BDNF and PSA-NCAM, and an increment in the expression of GAP43. These alterations were restricted to the regions related to dentate granule cells suggesting an interrelation. Therefore the impairment in dendritic arborisation and molecular plasticity is not a general feature of all Down syndrome principal neurons. Pharmacological manipulations of the levels of plasticity molecules could provide a way to restore granule cell morphology and function.
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Villarroya
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Ballestín
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: López-Hidalgo
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Mulet
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Blasco-Ibáñez
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Crespo
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.|Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain.|CIBERSAM: Spanish National Network for Research in Mental Health, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Nacher
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.|Genetics Department, Universitat de València, CIBERSAM, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gilabert-Juan
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain. emilio.varea@uv.es.
authors.forename: Emilio
authors.initials: E
authors.lastname: Varea
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019922:GAP-43 Protein / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006056:Golgi Apparatus / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D012794:Sialic Acids / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule