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J Neural Transm Suppl. 1999;57:221-32.

Serotonin (5-HT) in brains of adult patients with Down syndrome.

Seidl R, Kaehler ST, Prast H, Singewald N, Cairns N, Gratzer M, Lubec G.

Department of Pediatrics, University of Vienna, Austria.

Down syndrome (DS) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age dependent Alzheimer-type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. As the serotonergic system plays a well known role in integrating emotion, cognition and motor function, serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-acetic acid (5-HIAA) were investigated in post-mortem tissue samples from temporal cortex, thalamus, caudate nucleus, occipital cortex and cerebellum of adult patients with DS, Alzheimer's disease (AD) and controls by use of high performance liquid chromatography (HPLC). In DS, 5-HT was found to be age-dependent significantly decreased in caudate nucleus by 60% (DS: mean +/- SD 58.6 +/- 28.2 vs. Co: 151.7 +/- 58.4 pmol/g wet tissue weight) and in temporal cortex by about 40% (196.8 +/- 108.5 vs. 352.5 +/- 183.0 pmol/g), insignificantly reduced in the thalamus, comparable to controls in cerebellum, whereas occipital cortex showed increased levels (204.5 +/- 138.0 vs. 82.1 +/- 39.1 pmol/g). In all regions of DS samples, alterations of 5-HT were paralleled by levels of 5-HIAA, reaching significance compared to controls in thalamus and caudate nucleus. In AD, 5-HT was insignificantly reduced in temporal cortex and thalamus, unchanged in cerebellum, but significantly elevated in caudate nucleus (414.3 +/- 273.7 vs. 151.7 +/- 58.4 pmol/g) and occipital cortex (146.5 +/- 76.1 vs. 82.1 +/- 39.1 pmol/g). The results of this study confirm and extend putatively specific 5-HT dysfunction in basal ganglia (caudate nucleus) of adult DS, which is not present in AD. These findings may be relevant to the pathogenesis and treatment of cognitive and non-cognitive (behavioral) features in DS.

Life Sci. 1997;60(15):1231-7.

Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome.

Risser D, Lubec G, Cairns N, Herrera-Marschitz M.

Department of Pediatrics, University of Vienna, Austria.

Aspartate (ASP), glutamate (GLU), noradrenaline (NA), dopamine (DA) and its acidic metabolites DOPAC and HVA, serotonin (5-HT) and its metabolite 5-HIAA were simultaneously investigated in post-mortem tissue samples from right parahippocampal gyrus (temporal cortex) and frontal cortical pole (frontal cortex) of adults with Down syndrome (DS), and of neurologically healthy controls by use of high performance liquid chromatography (HPLC). In parahippocampal gyrus, ASP, GLU, NA, DOPAC and 5-HT levels were significantly decreased in patients with DS, compared to levels found in control subjects (approximately 50%). No significant changes were observed in frontal pole. ASP and GLU levels were significantly lower in parahippocampal gyrus than in frontal pole of DS, a regional distribution that could not be observed in control subjects. In conclusion, the results of this study suggest that the temporal cortex would be more affected than the frontal cortex in adult patients with DS, a finding in line with reports showing a marked hypometabolism and extensive cell loss in temporal cortex of DS, and with those showing that parahippocampal gyrus abnormality may correlate with the extent of mental retardation affecting this type of patients.