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. Abnormalities in brain development in Down Syndrome (DS) are described in a couple of morphological reports but the molecular mechanisms underlying abnormal wiring in fetal DS brain are not yet elucidated. We therefore performed a study using the proteomic approach to show differences in protein levels involved in the guidance of axons between control and DS brain in early prenatal life. Proteins obtained from autopsy of human fetal abortus were applied on 2-dimensional gel, identified and quantified. We quantified 5 members of the semaphorin/collapsin family, the dihydropyrimidinase related proteins 1-4 and the collapsin response mediator protein-5 (CRMP-5) in 8 DS and 7 control 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 levels of 2 of the 15 spots assigned to DRP-2 and increased levels of one spot assigned to DRP-3 and increased DRP-4 in DS brain. We conclude that as early as from the 19th 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 brain.
Weitzdoerfer
R
R
Department of Pediatrics, University of Vienna, Austria.
Fountoulakis
M
M
Lubec
G
G
D001921:Brain / Q000002:abnormalities / Q000378:metabolism*; D002465:Cell Movement; D004314:Down Syndrome / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009124:Muscle Proteins / Q000032:analysis / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C102926:DPYSL3 protein, human; C485780:DPYSL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C095114:collapsin response mediator protein-2