Increased incidence of intermittent hypoxemia in the Ts65Dn mouse model of Down syndrome

Das D., Medina B., BAKTIR M. A., Mojabi F., Fahimi A., Ponnusamy R., ...Daha Fazla

NEUROSCIENCE LETTERS, cilt.604, ss.91-96, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 604
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.neulet.2015.07.040
  • Dergi Adı: NEUROSCIENCE LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.91-96
  • Anahtar Kelimeler: Down syndrome, Ts65Dn mice, Alzheimer's disease, Hypoxemia, Hippocampus, Sleep apnea, CYTOCHROME-C-OXIDASE, SLEEP-APNEA, COGNITIVE DYSFUNCTION, ALZHEIMERS-DISEASE, NITRIC-OXIDE, HYPOXIA, EXPRESSION, INHIBITION, CHILDHOOD, UBIQUITIN
  • Erciyes Üniversitesi Adresli: Evet

Özet

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. Published by Elsevier Ireland Ltd.