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The Molecular Biology of Down Syndrome pp 221–232Cite as

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

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Summary

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.

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References

  • Andersson A, Sundman I, Marcusson J (1992) Age stability of human brain 5-HT terminals studied with 3H paroxetine binding. Gerontol 38: 127–132

    Article  CAS  Google Scholar 

  • Azmitia E, Whitaker-Azmitia P (1991) Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry 52 [Suppl 12]: 4–16

    PubMed  Google Scholar 

  • Bazelon M, Paine RS, Coeiw VA, Hunt P, Houck JC, Mahanand D (1967) Reversal of hypotonia in infants with Down’s syndrome by administration of 5-hydroxytry-ptophan. Lancet i: 1130–1133

    Article  CAS  Google Scholar 

  • Becker LE, Mito T, Takashima S, Onodera K (1991) Growth and development of the brain in Down syndrome. Prog Clin Biol Res 373: 133–152

    PubMed  CAS  Google Scholar 

  • Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, Perl DP, Schmeidler J, Kanof P, Davis KL (1995) Neurochemical correlates of dementia severity in Alzheimer’s disease: relative importance of the cholinergic deficits. J Neurochem 64: 749–760

    Article  PubMed  CAS  Google Scholar 

  • Bowen BB, Francis PT, Chessel IP, Webster MT (1994) Neurotransmission-the link integrating Alzheimer’s disease? Trends Neurosci 17: 149–150

    Article  PubMed  CAS  Google Scholar 

  • Casper RC (1998) Serotonin, a major player in regulation of feeding and affect. Biol Psychiatry 44: 795–797

    Article  PubMed  CAS  Google Scholar 

  • 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: 583–590

    Article  Google Scholar 

  • Chen CP, Alder JT, Bowen DM, Esiri MM, McDonald B, Hope T, Jobst KA, Francis PT (1996) Presynaptic serotonergic markers in community-acquired cases of Alzheimer’s disease: correlations with depression and neuroleptic medication. J Neurochem 66:1592–1598

    Article  PubMed  CAS  Google Scholar 

  • Coleman M (1971) Infantile spasms associated with 5-hydroxytryptophan administered in patients with Down’s syndrome. Neurol 21: 911

    Article  CAS  Google 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 749–794

    Google 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 263–293

    Google Scholar 

  • Gedye A (1990) Dietary increase in serotonin reduces self-injurious behaviour in a Down’s syndrome adult. J Ment Defic Res 34: 195

    PubMed  Google Scholar 

  • Gedye A (1991) Serotonergic treatment for aggression in a Down’s syndrome adult showing signs of Alzheimer’s disease. J Ment Defic Res 35: 247–258

    PubMed  Google 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: 99–104

    CAS  Google Scholar 

  • Godridge H, Reynolds GP, Czudek C, Calcutt NA, Benton M (1987) Alzheimer-like neurotransmitter deficits in adult Down’s syndrome brain tissue. J Neurol Neurosurg Psychiatry 50: 775–778

    Article  PubMed  CAS  Google Scholar 

  • Gottfries CG, Adolfsson R, Aquilonius SM, Carlsson A, Eckernas SA, Nordberg A, Oreland L, Svennerholm L, Wiberg A, Winblad B (1983) Biochemical changes in dementia disorders of Alzheimer type (AD/SDAT). Neurobiol Aging 4: 261–271

    Article  PubMed  CAS  Google Scholar 

  • Haxby JV (1989) Neuropsychological evaluation of adults with Down’s syndrome: patterns of selective impairment in nondemented old adults. J Ment Defic Res 33: 193–197

    PubMed  Google Scholar 

  • Holthoff-Detto K, Kessler J, Herholz K, Bonner H, Pietrzyk U, Wurker M, Ghaemi M, Wienhard K, Wagner R, Heiss WD (1997) Functional effects of striatal dysfunction in Parkinson disease. Arch Neurol 54: 145–150

    Article  PubMed  CAS  Google Scholar 

  • Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72: 165–229

    PubMed  CAS  Google 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 461–469

    Google Scholar 

  • Lauder JM (1993) Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Trends Neurosci 16: 233–240

    Article  PubMed  CAS  Google Scholar 

  • Lesch KP, Mössner R (1998) Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental and neurodgenerative disorders? Biol Psychiatry 44: 179–192

    Article  PubMed  CAS  Google Scholar 

  • Li T, Holmes C, Sham PC, Vallada H, Birkett J, Kirov G (1997) Allelic functional variation of serotonin transporter expression is a susceptibility factor for late-onset Alzheimer’s disease. Neuroreport 8: 683–686

    Article  PubMed  CAS  Google Scholar 

  • Lucki I (1998) The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44: 151–162

    Article  PubMed  CAS  Google Scholar 

  • Mann DMA, Yates PO (1986) Neurotransmitter deficits in Alzheimer’s disease and in other dementing disorders. Hum Neurobiol 5: 147–158

    PubMed  CAS  Google Scholar 

  • Mann DMA, Yates PO, Marcyniuk B, Ravindra CR (1985) Pathological evidence for neurotransmitter deficits in Down’s syndrome of middle age. J Ment Defic Res 29: 125–135

    PubMed  Google Scholar 

  • Mann DMA, Royston MC, Ravindra CR (1990) Some morphological observations on the brains of patients with Down’s syndrome: their relationship to age and dementia. J Neurol Sci 99: 153

    Article  PubMed  CAS  Google Scholar 

  • Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD). II. Standardisation of the neuropatho-logical assessment of Alzheimer’s Disease. Neurol 41: 479–486

    Article  CAS  Google Scholar 

  • Nadel L, Epstein CJ (eds) (1992) Down Syndrome and Alzheimer disease. Wiley-Liss, New York (Prog Clin Biol Res 379)

    Google Scholar 

  • Palmer AM, Stratmann GC, Procter AW, Bowen DM (1988) Possible neurotransmitter basis of behavioral changes in Alzheimer’s disease. Ann Neurol 23: 616–620

    Article  PubMed  CAS  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 193–221

    Google Scholar 

  • Reynolds GP, Godridge H (1985) Alzheimer-like brain monoamine deficits in adults with Down’s syndrome. Lancet ii: 1368–1369

    Article  Google Scholar 

  • Risser D, Lubec G, Cairns N, Herrera-Marschitz M (1997) Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. Life Sci 60: 1231–1237

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Gomez JA, de la Roza C, Machado A, Cano J (1995) The effect of age on the monoamines of the hypothalamus. Mech Ageing Dev 77: 185–195

    Article  PubMed  CAS  Google Scholar 

  • Singewald N, Kaehler S, Hemeida R, Philippu A (1997) Release of serotonin in the rat locus coeruleus: effects of cardiovascular, stressful and noxious stimuli. Eur J Neurosci 9: 556–562

    Article  PubMed  CAS  Google Scholar 

  • Staley JK, Malison RT, Innis RB (1998) Imaging of the serotonergic system: interactions of neuroanatomical and functional abnormalities of depression. Biol Psychiatry 44: 534–549

    Article  PubMed  CAS  Google 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: 359–364

    Google Scholar 

  • Tu JB, Zellweger H (1965) Blood-serotonin deficiency in Down’s syndrome. Lancet ii(7415): 715–716

    Article  Google Scholar 

  • Warren AC, Holroyd S, Folstein P (1989) Major depression in Down’s syndrome. Br J Psychiatry 155: 202–207

    Article  PubMed  CAS  Google Scholar 

  • Weise P, Koch R, Shaw KNF, Rosenfeld MJ (1974) The use of 5-HTP in the treatment of Down’s syndrome. Pediatr 54: 165–167

    CAS  Google Scholar 

  • Wisniewski KE, Kida E (1994) Abnormal neurogenesis and synaptogenesis in Down syndrome brain. Dev Brain Dysfunct 7: 289–301

    Google Scholar 

  • Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down syndrome. Ann Neurol 17: 278–282

    Article  PubMed  CAS  Google Scholar 

  • Yates CM, Simpson J, Maloney AFJ, Gordon A, Reid AH (1980) Alzheimer-like cholinergic deficiency in Down syndrome. Lancet Nov 1st: 979

    Google Scholar 

  • Yates CM, Simpson J, Gordon A, Maloney AFJ, Allison Y, Ritchie IM, Urquhart A (1983) Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down’s syndrome. Brain Res 280: 119–126

    Article  PubMed  CAS  Google Scholar 

  • Yates CM, Simpson J, Gordon A (1986) Regional brain 5-hydroxytryptamine levels are reduced in senile Down’s syndrome as in Alzheimer’s disease. Neurosci Lett 65:189–192

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    R. Seidl, M. Gratzer & Prof. Dr. G. Lubec

  2. Brain Bank, Institute of Psychiatry, University of London, London, UK

    N. Cairns

  3. Department of Pharmacology and Toxicology, University of Innsbruck, Austria

    S. T. Kaehler, H. Prast & N. Singewald

Authors
  1. R. Seidl
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  2. S. T. Kaehler
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  3. H. Prast
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  4. N. Singewald
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  5. N. Cairns
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  6. M. Gratzer
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  7. Prof. Dr. G. Lubec
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Editor information

Editors and Affiliations

  1. Universitäts-Kinderklinik, Wien, Österreich

    G. Lubec

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© 1999 Springer-Verlag Wien

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Seidl, R. et al. (1999). Serotonin (5-HT) in brains of adult patients with Down Syndrome. In: Lubec, G. (eds) The Molecular Biology of Down Syndrome. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6380-1_14

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  • DOI: https://doi.org/10.1007/978-3-7091-6380-1_14

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83377-3

  • Online ISBN: 978-3-7091-6380-1

  • eBook Packages: Springer Book Archive

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