Oxidative stress and disturbed glutamate transport in hereditary nucleotide repair disorders

Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are heredita ry DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that a re produced by oxidative stress and glutamate transporters (which can contr ibute to prevention of glutamate neurotoxicity) in the brains of 5 autopsie d patients each of XPA. CS, and control groups, All oxidative products, inc luding nitrotyrosine, advanced glycation end product, and 4-hydroxy-2-nonen al-modified protein (HNE) were deposited in large amounts in the globus pal lidus of CS patients compared to XPA patients. They were frequently recogni zed in the pseudocalcified foci and free minerals in the neuropil, and more rarely in foamy spheroids. In addition, the deposition of UNE was observed also in hippocampal and cerebellar dentate neurons of both CS and XPA pati ents. The expression of glial glutamate transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS patients and 3 XPA patients. They w ere also altered in the cerebellar cortex in most of the CS patients. These data suggest that oxidative stress and disturbed glutamate transport may b e involved in pallidal and/or cerebellar degeneration in hereditary nucleot ide repair disorders.