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Down Syndrome Abstract
of the Month: July 2002

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

Weitzdoerfer R, Dierssen M, Fountoulakis M, Lubec G
J Neural Transm Suppl 2001;(61):59-70

Dept. of Pediatrics, University of Vienna, Austria

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Information on fetal brain in Down Syndrome (DS) is limited and there are only few histological, mainly anecdotal reports and no systematic study on the wiring of the brain in early prenatal life exists. Histological methods are also hampered by inherent problems of morphometry of neuronal structures. It was therefore the aim of the study to evaluate neuronal loss, synaptic structures and dendritic spines in the fetus with Down Syndrome as compared to controls by biochemical measurements.
Method: 2 dimensional electrophoresis with subsequent mass spectroscopical identification of spots and their quantification with specific software was selected. This technique identifies proteins unambiguously and concomitantly on the same gel. Fetal cortex samples were taken at autopsy with low post-mortem time, homogenized and neuron specific enolase (NSE) determined as a marker for neuronal density, the synaptosomal associated proteins alpha SNAP [soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein], beta SNAP, SNAP 25 and the channel associated protein of synapse 110 (chapsyn 110) as markers for synaptosomal structures and drebrin (DRB) as marker for dendritic spines. NSE, chapsyn 110 and beta SNAP were comparable in the control fetus panel and in Down Syndrome fetuses. Drebrin was significantly and remarkably reduced and not even detectable in several Down Syndrome brain samples. Quantification of SNAP 25 revealed significantly reduced values in DS cortex and alpha SNAP was only present in half of the DS individuals.
Conclusion: at the time point of about 19 weeks of gestation (early second trimester) no neuronal loss can be detected but drebrin, a marker for dendritic spines and synaptosomal associated proteins alpha SNAP and SNAP 25 were significantly reduced indicating impaired synaptogenesis. Early dendritic deterioration maybe leading to the degeneration of the dendritic tree and arborization, which is a hallmark of Down Syndrome from infancy.

My comments:

This paper was produced by the group of researchers that are currently leading the field in the study of brain development in Down syndrome. It was published as part of a collection of 30 papers on this topic at the end of 2001 (Protein Expression in Down Syndrome Brain, ed. G Lubec, 2001), and is an example of current research. The more we learn about the microanatomy and biochemistry of the brain, the more likelihood that we will find the actual cause of mental retardation in Down syndrome.

Along with previous reports of abnormalities of placement of brain cells (neurons) in the cortex and abnormal development of synapses (connections between neurons), I hope this puts an end to the myth that infants with Down syndrome are born with normal brains.

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