Die Neurotransmitter des Gehirns im Alter

  • O. Hornykiewicz
Part of the Verhandlungen der Deutschen Gesellschaft für Neurologie book series (VDGNEUROLOGIE, volume 5)


Im Jahre 1902 veröffentlichte der britische Neurologe Gowers einen Aufsatz, betitelt: „Lecture on Abiotrophy”, worin er als einer der ersten den Gedanken klar aussprach, daß Altern mit selektivem Verfall (Abiotrophie) bestimmter Neuronensysteme des Zentralnervensystems einhergehen könnte [20]. Im folgenden soll das Verhalten der wichtigsten heute bekannten Neurotransmitter im Gehirn des alternden, neurologisch gesunden Menschen kritisch untersucht werden.


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  1. 1.
    Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979) Post-mortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and a review of the literature. J Neural Transm 45: 81–105PubMedCrossRefGoogle Scholar
  2. 2.
    Allen SJ, Benton JS, Godhardt MJ et al. (1983) Biochemical evidence of selective nerve cell changes in the normal ageing human and rat brain. J Neurochem 41: 256–265PubMedCrossRefGoogle Scholar
  3. 3.
    Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417PubMedCrossRefGoogle Scholar
  4. 4.
    Bennett JP, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Synder SH (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 36: 927–934PubMedCrossRefGoogle Scholar
  5. 5.
    Bertler A (1961) Occurrence and localization of catechol amines in the human brain. Acta Physiol Scand 51: 97–107CrossRefGoogle Scholar
  6. 6.
    Bird ED, Iversen LL (1974) Huntington’s chorea: Post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain 97: 457–472PubMedCrossRefGoogle Scholar
  7. 7.
    Bird ED, Spokes EG, Iversen LL (1979) Brain norepinephrine and dopamine in schizophrenia (technical comment). Science 204: 93–94PubMedCrossRefGoogle Scholar
  8. 8.
    Brody H (1976) An examination of cerebral cortex and brainstem aging. In: Terry RD, Gershon S (eds) Neurobiology of aging. Raven Press, New York, p 177Google Scholar
  9. 9.
    Bucht G, Adolfsson R, Gottfries CG, Roos BE, Winblad B (1981) Distribution of 5-hydroxy-tryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation. J Neural Transm 51: 185–203PubMedCrossRefGoogle Scholar
  10. 10.
    Bugiani O, Perdelli F, Salvarani S, Leonardi A, Mancardi GL (1980) Loss of striatal neurons in Parkinson’s disease: A cytometric study. Eur Neurol 19: 339–344PubMedCrossRefGoogle Scholar
  11. 11.
    Carlsson A, Winblad B (1976) Influence of age and time interval between death and autopsy on dopamine and 3-methoxytyramine levels in human basal ganglia. J Neural Transm 38: 271–276PubMedCrossRefGoogle Scholar
  12. 12.
    Carlsson A, Adolfsson R, Aquilonius SM, Gottfries CG, Oreland L, Svennerholm L, Winblad B (1980) Biogenic amines in human brain in normal aging, senile dementia, and chronic alcoholism. In: Goldstein M et al. (eds) Ergot compounds and brain function: Neuroendocrine and neuropsychiatric aspects. Raven Press, New York, p 295Google Scholar
  13. 13.
    Cohen G (1983) The pathobiology of Parkinson’s disease: Biochemical aspects of dopamine neuron senescence. J Neural Transm (Suppl) 19: 89–103Google Scholar
  14. 14.
    Côté JT, Kremzner LT (1974) Changes in neurotransmitter systems with increasing age in human brain. Trans Am Soc Neurochem 5: 83Google Scholar
  15. 15.
    Coyle JT, Price DL, DeLong MR (1983) Alzheimer’s disease: A disorder of cortical cholinergic innervation. Science 219: 1184–1190PubMedCrossRefGoogle Scholar
  16. 16.
    Coyle JT, Singer H, Beaulieu M, Johnston MV (1984) Development of central neurotransmitter-specified neuronal systems: Implications for pédiatric neuropsychiatrie disorders. Acta Neurol Scand 69: 1–11Google Scholar
  17. 17.
    Crow TJ, Baker HF, Cross AJ et al. (1979) Monoamine mechanisms in chronic schizophrenia: Post mortem neurochemical findings. Br J Psychiatry 134: 249–256PubMedCrossRefGoogle Scholar
  18. 18.
    Davies P (1981) Theoretical treatment possibilities for dementia of the Alzheimer type: The cholinergic hypothesis. In: Crook T, Gershon S (eds) Strategies for the development of an effective treatment for senile dementia. Mark Powley, New Canaan CT, p 19Google Scholar
  19. 19.
    Davies P (1988) Neurochemistry of human aging: Conceptual and practical problems. In: Kent B, Butler RN (eds) Human aging research: Concepts and techniques. Raven Press, New York, p 277Google Scholar
  20. 20.
    Gowers WR (1902) Lecture of abiotrophy. Lancet 1: 1003–1007Google Scholar
  21. 21.
    Graham DG (1984) Catecholamine toxicity: A proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson’s disease. Neurotoxicology 5: 83–96PubMedGoogle Scholar
  22. 22.
    Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. Trends Neurosci 8: 22–26CrossRefGoogle Scholar
  23. 23.
    Hornykiewicz O (1983) Parkinson’s disease and the aging basal ganglia. In: Gispen WH, Traber J (eds) Aging of the brain. Elsevier, Amsterdam, p 253Google Scholar
  24. 24.
    Hornykiewicz O (1985) Brain dopamine and ageing. Interdiscipl Topics Gerontol 19: 143–155Google Scholar
  25. 25.
    Langsten JW, Längsten EB, Irwin I (1984) MPTP-induced parkinsonism in human and non-human primates — clinical and experimental aspects. Acta Neurol Scand 70 (Suppl) 100: 49–54Google Scholar
  26. 26.
    Lloyd KG, Hornykiewicz O (1972) Occurrence and distribution of L-DOPAS decarboxylase in the human brain. J Neurochem 19: 1549–1559PubMedCrossRefGoogle Scholar
  27. 27.
    Lloyd KG, Davidson L, Hornykiewicz O (1975) The neurochemistry of Parkinson’s disease: Effect of L-DOPA therapy. J Pharmacol 195: 453–464Google Scholar
  28. 28.
    Mackay AVP, Davies P, Dewar AJ, Yates CM (1978) Regional distribution of enzymes associated with neurotransmission by monoamines, acetylcholine and GABA in the human brain. J Neurochem 30: 827–839PubMedCrossRefGoogle Scholar
  29. 29.
    Mackay AVP, Yates CM, Wright A, Hamilton P, Davies P (1978) Regional distribution of monoamines and their metabolites in the human brain. J Neurochem 30: 841–848PubMedCrossRefGoogle Scholar
  30. 30.
    Marcusson J, Morgan DG, Winblad B, Finch CE (1984) Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of S-2A sites with age. Brain Res 311: 51–56Google Scholar
  31. 31.
    Marcusson J, Oreland L, Winblad B (1984) Effect of age on human brain serotonin (S-l) binding sites. J Neurochem 43: 1699–1705PubMedCrossRefGoogle Scholar
  32. 32.
    McGeer E, McGeer PL (1976) Neurotransmitter metabolism in the aging brain. In: Terry RD, Gershon S (eds) Neurobiology of aging. Aging, Vol 3. Raven Press, New York, p 389Google Scholar
  33. 33.
    McGeer EG (1978) Aging and neurotransmitter metabolism in the human brain. In: Katzman R, Terry RD, Bick KL (eds) Alzheimer’s disease: Senile dementia and related disorders. Aging, Vol 7. Raven Press, New York, p 427Google Scholar
  34. 34.
    McGeer EG, Fibiger HC, McGeer PL, Wickson V (1971) Aging and brain enzymes. Exp Gerontol 6: 391–396PubMedCrossRefGoogle Scholar
  35. 35.
    McGeer PL, McGeer EG (1976) Enzymes associated with the metabolism of catecholamines acetylcholine and GABA in human controls and patients with Parkinson’s disease and Hunting-ton’s chorea. J Neurochem 26: 65–76PubMedGoogle Scholar
  36. 36.
    McGeer PL, McGeer EG, Suzuki JS (1977) Aging and extrapyramidal function. Arch Neurol 34: 33–35PubMedCrossRefGoogle Scholar
  37. 37.
    McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T (1984) Aging, Alzheimer’s disease, and the cholinergic system of the basal forebrain. Neurology 34: 741–745PubMedCrossRefGoogle Scholar
  38. 38.
    Minard FN, Mushahwar IK (1966) Synthesis of gamma-aminobutyric acid from a pool of gluta-mic acid in brain after decapitation. Life Sci 5: 1409–1413PubMedCrossRefGoogle Scholar
  39. 39.
    Moses SG, Robins E (1975) Regional distribution of norepinephrine and dopamine in brains of depressive suicides and alcoholic suicides. Psychopharmacol Comm 1: 327–337Google Scholar
  40. 40.
    Nies A, Robinson DS, Davis JM, Ravaris L (1973) Changes in monoamine oxidase with aging. In: Eisdorfer C, Farm WE (eds) Psychopharmacology and aging. Plenum Press, New York, p 41CrossRefGoogle Scholar
  41. 41.
    O’Neill C, Marcusson J, Nordberg A, Winblad B (1987) The influence of age on neurotrans-mitters in the human brain. In: Govoni S, Battaini F (eds) Modification of cell to cell signals during normal and pathological aging. NATO ASI Series, Vol 19. Springer, Berlin Heidelberg New York Tokyo, p 183CrossRefGoogle Scholar
  42. 42.
    Pare CMB, Yeung DPH, Price K, Stacey RS (1969) 5-Hydroxytryptamine, noradrenaline and dopamine in brainstem, hypothalamus, and caudate nucleus of controls and of patients committing suicide by coal-gas poisoning. Lancet 11: 133–135CrossRefGoogle Scholar
  43. 43.
    Perry EK, Perry RH, Gibson PH, Blessed G, Tomlinson BE (1977) A cholinergic connection between normal aging and senile dementia in the human hippocampus. Neurosci Lett 6: 85–89PubMedCrossRefGoogle Scholar
  44. 44.
    Perry EK, Perry RH, Tomlinson BE (1982) The influence of agonal status on some neurochemical activities of postmortem human brain tissue. Neurosci Lett 29: 303–307PubMedCrossRefGoogle Scholar
  45. 45.
    Riederer P, Wuketich S (1976) Time course of nigrostriatal degeneration in Parkinson’s disease. J Neural Transm 38: 277–301PubMedCrossRefGoogle Scholar
  46. 46.
    Rinne UK, Sonninen V (1973) Brain catecholamines and their metabolites in parkinsonian patients. Arch Neurol 28: 107–110PubMedCrossRefGoogle Scholar
  47. 47.
    Robinson DS, Davis JM, Nies A, Ravaris CL, Sylwester D (1971) Relation of sex and aging to monoamine oxidase activity of human brain, plasma and platelets. Arch Gen Psychiatry 24: 536–539PubMedCrossRefGoogle Scholar
  48. 48.
    Robinson DS, Davis JM, Nies A et al. (1972) Aging, monoamines, and monoamine-oxidase levels. Lancet 1: 290–291PubMedCrossRefGoogle Scholar
  49. 49.
    Robinson DS, Sourkes TL, Nies A, Harris LS, Spector S, Bartlett DL, Kaye IS (1977) Monoamine metabolism in human brain. Arch Gen Psychiatry 34: 89–92PubMedCrossRefGoogle Scholar
  50. 50.
    Rossor MN, Iversen LL, Reynolds GP, Mountjoy CQ, Roth M (1984) Neurochemical characteristics of early and late onset types of Alzheimer’s disease. Br Med J 288: 961–964CrossRefGoogle Scholar
  51. 51.
    Severson JA, Marcusson J, Winblad B, Finch CE (1982) Age-correlated loss of dopaminergic binding sites in human basal ganglia. J Neurochem 39: 1623–1631PubMedCrossRefGoogle Scholar
  52. 52.
    Severson JA, Marcusson JO, Osterburg HH, Finch CE, Winblad B (1985) Elevated density of 3H imipramine binding in aged human brain. J Neurochem 45: 1382–1389PubMedCrossRefGoogle Scholar
  53. 53.
    Spokes EGS, Garrett NJ, Iversen LL (1979) Differential effects of agonal status on measurements of GABA and glutamate decarboxylase in human post-mortem brain tissue from control and Huntington’s chorea subjects. J Neurochem 33: 773–778PubMedCrossRefGoogle Scholar
  54. 54.
    Wilk S, Stanley M (1978) Dopamine metabolites in human brain. Psychopharmacology 57: 77–81PubMedCrossRefGoogle Scholar
  55. 55.
    Winblad B, Hardy J, Bäckman L, Nilsson SG (1985) Memory function and brain biochemistry in normal aging and in senile dementia. Ann New York Acad Sci 444: 255–268CrossRefGoogle Scholar
  56. 56.
    Winblad B, Bucht G, Gottfries CG, Roos BE (1979) Monoamines and monoamine metabolites in brains from demented schizophrenics. Acta Psychiat Scand 60: 17–28PubMedCrossRefGoogle Scholar
  57. 57.
    Wong DF, Wagner HN, Dannals RF et al. (1984) Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 226: 1393–1396PubMedCrossRefGoogle Scholar
  58. 58.
    Zelnik N, Angel I, Paul SM, Kleinman JE (1986) Decreased density of human striatal dopamine uptake sites with age. Eur J Pharmacol 126: 175–176PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1989

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  • O. Hornykiewicz

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