title: Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis.
abstract: Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5'BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5'BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice.
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, 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 ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Ballestín
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Vega
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Blasco-Ibáñez
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, 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 ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, Spain; Fundación Investigación Hospital Clínico de Valencia, INCLIVAValència, Spain; CIBERSAM, Spanish National Network for Research in Mental HealthValència, Spain; Genetics Department, CIBERSAM, Universitat de ValènciaValència, 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 ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, Spain; Fundación Investigación Hospital Clínico de Valencia, INCLIVAValència, Spain; CIBERSAM, Spanish National Network for Research in Mental HealthValència, Spain; Genetics Department, CIBERSAM, Universitat de ValènciaValència, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Nácher
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de ValènciaValència, Spain; Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (BIOTECMED), Universitat de ValènciaValència, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Varea
keywords: Ki67; Ts65Dn mice; adult neurogenesis; doublecortin; down syndrome; hippocampus; olfactory bulb