Down's syndrome astrocytes have greater antioxidant capacity than euploid astrocytes

Down's syndrome (trisomy 21) brain tissue is considered to be susceptible to oxidative injury, mainly because its increased Cu/Zn-superoxide dismutase (SOD1) activity is not followed by an adaptive rise in hydrogen peroxide metabolizing enzymes. In vitro, trisomic neurons suffer oxidative stress and degenerate. We studied the response of trisomy 21 neuron and astrocyte cultures to hydrogen peroxide injury and found that they were, respectively, more and less vulnerable than their euploid counterparts. Differences were detected 24 h after exposures in the region of 50 μM and 500 μM hydrogen peroxide for neuron and astrocyte cultures, respectively. Cytotoxicity results were paralleled by a decrease in cellular glutathione. In addition, trisomic astrocytes showed a lower basal content of superoxide ion and a higher clearance of hydrogen peroxide from the culture medium. In the presence of hydrogen peroxide, trisomic astrocytes maintained their concentration of intracellular superoxide and hydroperoxides at a lower level than euploid astrocytes. Consistent with these results, trisomic astrocytes in neuron coculture were more neuroprotective than euploid astrocytes against hydrogen peroxide injury. We suggest that SOD1 overexpression has beneficial effects on astrocytes, as it does in other systems with similarly high disposal of hydroperoxides. In addition to a higher enzymatic activity of SOD1, cultures of trisomic astrocytes showed slightly higher glutathione reductase activity than euploid cultures. Thus, trisomy 21 astrocytes showed a greater antioxidant capacity against hydrogen peroxide than euploid astrocytes, and they partially counteracted the oxidative vulnerability of trisomic neurons in culture.