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

Down syndrome (DS) is a genetic disease with developmental brain abnormalit ies resulting in early mental retardation and precocious, age dependent Alz heimer-type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. As the serotoner gic system plays a well known role in integrating emotion, cognition and mo tor function, serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-ac etic acid (5-HIAA) were investigated in post-mortem tissue samples from tem poral cortex, thalamus, caudate nucleus, occipital cortex and cerebellum of adult patients with DS, Alzheimer's disease (AD) and controls by use of hi gh performance liquid chromatography (HPLC). In DS, 5-HT was found to be ag e-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 t emporal cortex by about 40% (196.8 +/- 108.5 vs. 352.5 +/- 183.0 pmol/g), i nsignificantly reduced in the thalamus, comparable to controls in cerebellu m, 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 i n 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 basa l 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.