The Molecular Synaptosomal Deficit in Down Syndrome Starts Early in Life

Abstract

Information about brain abnormalities in early prenatal life leading to or representing mental retardation in Down syndrome (DS) is limited. Synaptic dysgenesis was described and is considered the morphological correlate of mental retardation. The availability of appropriate fetal brain samples along with the advent of proteomic technologies unambiguously identifying proteins concomitantly made us study synaptosomal structures at the molecular level in the fetal cortex of controls and DS fetuses. Cortical tissue of seven controls (mean 18.8 weeks of gestation) and eight DS fetuses (mean 19.8 weeks of gestation) was homogenized, proteins were extracted and run on two-dimensional gel electrophoresis followed by mass spectrometrical analysis using MALDI-TOF (matrix-assisted laser desorption ionization – time of flight). Levels of synaptic proteins N-ethylmaleimide-sensitive fusion protein (controls: mean 0.030 ± 0.015; DS: mean 0.011 ± 0.008 O.D.), synaptotagmin I (controls: mean 0.038 ± 0.021; DS: mean 0.010 ± 0.002 O.D.) and septin 3 (controls: mean 0.061 ± 0.002; DS: mean 0.019 ± 0.012 O.D.) were significantly decreased in brains of fetuses with DS. It is concluded that an altered expression of synaptosomal proteins at the time of the early second trimester of gestation may form the structural basis for the brain deficit in DS early in life.