Serotonin (5-HT) in brains of adult patients with Down Syndrome
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 ± 58.4pmol/g wet tissue weight) and in temporal cortex by about 40% (196.8 ± 108.5 vs. 352.5 ± 183.0pmol/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 ± 58.4pmol/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.
KeywordsHigh Performance Liquid Chromatography Down Syndrome Caudate Nucleus Occipital Cortex Down Syndrome Patient
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- Celeda P, Artigas F (1993) Effects of local and systemic MAO inhibitors on extracellular brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the frontal cortex and raphe nuclei of freely moving rats. An in vivo microdialysis study. Naunyn Schmiedebergs Arch Pharmacol 347: 583–590CrossRefGoogle Scholar
- Epstein CJ (1995) Down Syndrome (Trisomy 21). In: Scriver SR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 749–794Google Scholar
- Frazer A, Hensler JG (1999) Serotonin. In: Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds) Basic neurochemistry, molecular, cellular and medical aspects, 6th edn. Lippincott Raven, Philadelphia New York, pp 263–293Google Scholar
- Geldmacher DS, Lerner AJ, Voci JM, Noelker EA, Somple LC, Whitehouse PJ (1997) Treatment of functional decline in adults with Down syndrome using seletive serotonin-reuptake inhibitor drugs. J Geriatr Psychiat Neurol 10: 99–104Google Scholar
- Jacobs B, Fornai C (1995) Serotonin and behavior, a general hypothesis. In: Bloom F, Kupfer D (eds) Psychopharmacology: the fourth generation of progess. Raven Press, New York, pp 461–469Google Scholar
- Nadel L, Epstein CJ (eds) (1992) Down Syndrome and Alzheimer disease. Wiley-Liss, New York (Prog Clin Biol Res 379)Google Scholar
- Procter AW, Francis PT, Chen CPLH, Chessel IP, Dijk S, Clarke NA, Webster MT, Bowen DM (1995) The neurochemical pathology of Alzheimer’s disease. In: Allen SJ, Dawbarn D (eds) Neurobiolgy of Alzheimer disease. BIOS Scientific Publ, Oxford, pp 193–221Google Scholar
- Tierney MC, Fisher RH, Lewis AJ, Torzitto ML, Snow WG, Reid DW, Nieuwstraten P, Van Rooijen LAA, Derks HJGM, Van Wijk R, Bischop A (1998) The NINCDA-ADRDA work group criteria for the clinical diagnosis of probable Alzheimer’s disease. Neurol 38: 359–364Google Scholar
- Weise P, Koch R, Shaw KNF, Rosenfeld MJ (1974) The use of 5-HTP in the treatment of Down’s syndrome. Pediatr 54: 165–167Google Scholar
- Wisniewski KE, Kida E (1994) Abnormal neurogenesis and synaptogenesis in Down syndrome brain. Dev Brain Dysfunct 7: 289–301Google Scholar
- Yates CM, Simpson J, Maloney AFJ, Gordon A, Reid AH (1980) Alzheimer-like cholinergic deficiency in Down syndrome. Lancet Nov 1st: 979Google Scholar