Aim: 

Down syndrome, or trisomy 21, is a chromosomal disorder caused by the presence of all or part of an extra 21^st chromosome. The clinical features include mental retardation and typical phenotypic features. Overexpression of several genes localized in chromosome 21 has been linked to mitochondrial energy production, free radicals detoxification, such as Cu/Zn superoxide dismutase, neuronal death during nervous system generation and neuropathophysiology of Alzheimer disease. In previous "in vivo" studies carried out in our laboratory we showed that there is an oxidative stress associated to Down syndrome, measured by an increase of 8-OHdG levels and GSSG/GSH ratio in blood.

Methods: 

We performed studies in vitro using fibroblasts during different states of cell cycle from Down syndrome fetuses and control fetuses without chromosomopathies. In vivo studies from Down syndrome volunteers and age-matched were also performed. We characterized the oxidative stress profile and indicators of apoptosis.

Results: 

Our results indicated than in patients an increase in plasma cytochrome c levels and in p53 expression in peripheral blood leukocytes takes place. In cultured fibroblasts we found a decrease in GSH levels in cells from Down syndrome fetuses. We measure mRNA levels of antioxidant and glutathione synthesis enzymes. The expression of SOD-Mn and Bcl-2 was increased in fibroblasts from Down syndrome. These results were confirmed by western-blotting as expression of these proteins was also increased.

Conclusion: 

There is a considerable literature supporting a major role of oxidative stress in Down syndrome and a predisposition to apoptosis according to our results from both patients, and fibroblasts.