title: Increased incidence of intermittent hypoxemia in the Ts65Dn mouse model of Down syndrome.
abstract: In addition to nervous system, cardiovascular and respiratory systems are primarily affected in Down syndrome (DS). The Ts65Dn mouse model is widely used to recapitulate cognitive dysfunction in DS. While these mice consistently show failure in learning and memory along with functional and structural abnormalities in the hippocampal region, the underlying mechanisms behind cognitive dysfunction remain to be fully elucidated. Convergent evidence implicates chronic episodes of hypoxemia in cognitive dysfunction in people with DS. Using an infra-red detection system to assess oxygen saturation in free-moving mice, we assessed arterial blood oxygenation in both adolescent and adult Ts65Dn mice and found a significant increase in the incidence of hypoxemia in both groups. Notably, the severity of hypoxemia increased during the dark cycle, suggesting a link between hypoxemia and increased motor activity. Postmortem analysis showed significant increase in the expression of mitochondrial Cox4i2, the terminal enzyme of the mitochondrial respiratory chain and oxygen response element. Altogether these data suggest early and chronic occurrence of hypoxemia in the Ts65Dn mouse model of DS, which can contribute to cognitive dysfunction in these mice.
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA.
authors.forename: Devsmita
authors.initials: D
authors.lastname: Das
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Medina
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA.
authors.forename: Mehmet Akif
authors.initials: MA
authors.lastname: Baktir
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA.
authors.forename: Fatemeh S
authors.initials: FS
authors.lastname: Mojabi
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA.
authors.forename: Atoossa
authors.initials: A
authors.lastname: Fahimi
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Ponnusamy
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA. Electronic address: asalehi@stanford.edu.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salehi
mesh_terms: D000367:Age Factors; D000818:Animals; D003624:Darkness; D018891:Dentate Gyrus / Q000201:enzymology; D004314:Down Syndrome / Q000097:blood* / Q000201:enzymology* / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000097:blood* / Q000201:enzymology*; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology; D010100:Oxygen / Q000097:blood*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D003576:Electron Transport Complex IV; D010100:Oxygen
keywords: Alzheimer’s disease; Down syndrome; Hippocampus; Hypoxemia; Sleep apnea; Ts65Dn mice