Abstract
Down syndrome (DS) with an additional copy of the human chr.21 (HSA21) is characterized by various phenotypes, such as intellectual disability and neurological abnormalities. Although it is widely accepted that a high level of oxidative stress (OS) is involved in DS symptoms, the actual role of elevated OS on DS phenotypes remains unclear. Among the genes on HSA21, amyloid-β precursor protein (App) and Cu/Zn superoxide dismutase (Sod1) are thought to be involved in the elevated OS and neurological abnormalities commonly described in DS. Ts1Cje mice, a widely used genetic model of DS, exhibit some of the abnormalities of DS patients, including cognitive impairment with electrophysiological abnormality, despite the exclusion of App and Sod1 in their trisomic region. We demonstrated a high level of OS in Ts1Cje mice, suggesting that the trisomic gene(s) other than App and Sod1 increase the OS in Ts1Cje mice. In this symposium, I intend to introduce our latest results, which suggest the accumulation of copper in the Ts1Cje mouse brain, and discuss the pathophysiological significance of copper in relation to the abnormalities observed in DS patients, particularly elevated OS.
