Aberrant expression of dihydropyrimidinase related proteins-2,-3 and-4 in fetal Down Syndrome brain

Pathfinding of growing axons to reach their target during brain development is a subtle process needed to build up contacts between neurons. Abnormali ties in brain development in Down Syndrome (DS) are described in a couple o f morphological reports but the molecular mechanisms underlying abnormal wi ring in fetal DS brain are not yet elucidated. We therefore performed a stu dy using the proteomic approach to show differences in protein levels invol ved in the guidance of axons between control and DS brain in early prenatal life. Proteins obtained from autopsy of human fetal abortus were applied o n 2-dimensional gel, identified and quantified. We quantified 5 members of the sernaphorin/collapsin family, the dihydropyrimidinase related proteins 1-4 and the collapsin response mediator protein-5 (CRMP-5) in 8 DS and 7 co ntrol cortex samples. DRP-1 and CRMP-5 levels were comparable in the control and DS samples. Evaluation of DRP-2, DRP-3 and DRP-4 revealed significantly decreased level s of 2 of the 15 spots assigned to DRP-2 and increased levels of one spot a ssigned to DRP-3 and increased DRP-4 in DS brain. We conclude that as early as from the 19(th) week of gestation pathfinding cues of the outgrowing axons are impaired in DS. These findings may help to elucidate mechanisms leading to abnormalities in neural migration of DS br ain.