Fetal life in Down Syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure

Information on fetal brain in Down Syndrome (DS) is limited and there are o nly few histological, mainly anecdotal reports and no systematic study on t he wiring of the brain in early prenatal life exists. Histological methods are also hampered by inherent problems of morphometry of neuronal structure s. It was therefore the aim of the study to evaluate neuronal loss, synapti c structures and dendritic spines in the fetus with Down Syndrome as compar ed to controls by biochemical measurements. 2 dimensional electrophoresis w ith subsequent mass spectroscopical identification of spots and their quant ification with specific software was selected. This technique identifies pr oteins unambiguously and concomitantly on the same gel. Fetal cortex sample s were taken at autopsy with low post-mortem time, homogenized and neuron s pecific enolase (NSE) determined as a marker for neuronal density, the syna ptosomal associated proteins alpha SNAP [soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein], beta SNAP, SNAP 25 and the channel assoc iated protein of synapse 110 (chapsyn 110) as markers for synaptosomal stru ctures and drebrin (DRB) as marker for dendritic spines. NSE, chapsyn 110 a nd beta SNAP were comparable in the control fetus panel and in Down Syndrom e fetuses. Drebrin was significantly and remarkably reduced and not even detectable in several Down Syndrome brain samples. Quantification of SNAP 25 revealed si gnificantly reduced values in DS cortex and alpha SNAP was only present in half of the DS individuals. We conclude that at the time point of about 19 weeks of gestation (early se cond trimester) no neuronal loss can be detected but drebrin, a marker for dendritic spines and synaptosomal associated proteins alpha SNAP and SNAP 2 5 were significantly reduced indicating impaired synaptogenesis. Early dend ritic deterioration maybe leading to the degeneration of the dendritic tree and arborization, which is a hallmark of Down Syndrome from infancy.