Review Article

Age-Related Neurodegeneration and Memory Loss in Down Syndrome

Figure 4

(a) Superarray (SABiosciences, Frederick, MD) against oxidative stress and inflammatory markers was used on hippocampal tissue from pooled samples (3 per group) of Ts65Dn and Normosomic mice at 4, 8, 10, and 13 months of age. Note the increased expression in APP and SOD-1 due to increased gene dosage of these genes. However, glutathione peroxidase 1 and 3 (GPX 1 and 3), as well as catalase levels, were not increased to the same extent. Further investigation of the glutathione enzymatic pathway revealed increased GSSG:GSH ratio in Ts65Dn compared to normosomic brain (b), suggesting, a compensatory processing of free radicals, but not sufficient to eliminate peroxidation in neurons. Glutathione exists in two forms: GSH (reduced form) and GSSG (oxidized form). Normally the relationship between these two forms is 1 : 10 in healthy cells. (c) Schematic representation of the ROS scavengers, demonstrating that elevated SOD levels may lead to increased H2O2 levels, leading to enhanced stress on the glutathione and catalase pathways. Data were not published previously.
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(a) Hippocampal gene expression
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(b) Oxidized glutathione in cortex at 4 mo
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(c) Scavenger pathway