Journal of Neural Transmission

, Volume 103, Issue 1–2, pp 101–115 | Cite as

Brain monoaminergic and neuropeptidergic variations in human aging

  • B. Arranz
  • K. Blennow
  • R. Ekman
  • A. Eriksson
  • J. -E. Månsson
  • J. Marcusson
Parkinson's Disease and Allied Conditions


The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydr-oxyphenylacetic acid (DOPAC), and the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control subjects, aged 16–75 years. After correcting for postmortem interval, significant decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA concentrations were obtained with advancing age. The involvement of the monoaminergic system in several functional abnormalities appearing in senescence is suggested. Furthermore, evidence is given of the participation of the peptidergic systems in the aging process.


Human brain aging monoamines neuropeptide Y somatostatin corticotropin-releasing factor HPLC 


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  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: 81–105Google Scholar
  2. Allard P, Marcusson J (1989) Age-correlated loss of dopamine uptake labeled with [3H]GBR-12935 in human putamen. Neurobiol Aging 10: 661–664Google Scholar
  3. Andersson A, Sundman I, Marcusson J (1992) Age stability of human brain 5-HT terminals studied with [3H]paroxetine binding. Gerontology 38: 127–132Google Scholar
  4. Arranz B, Eriksson A, Mellerup E, Plenge P, Marcusson J (1993) Effect of aging in human cortical pre- and postsynaptic serotonin binding sites. Brain Res 620: 163–166Google Scholar
  5. Beal MF, Frank RC, Ellison DW, Martin JB (1986) The effect of neuropeptide Y in striatal catecholamines. Neurosci Lett 71: 118–125Google Scholar
  6. Beskow J, Gottfries CG, Roos BE (1976) Determination of monoamine and monoamine metabolites in the human brain: post-mortem studies in a group of suicides and in a control group. Acta Psychiatr Scand 53: 7–20Google Scholar
  7. Bowen DM, Najlerahim A, Procter AW, Francis PT (1989) Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of later life. Proc Natl Acad Sci 86: 9504–9508Google Scholar
  8. Bucht G, Adolfsson R, Gottfries CG, Roos BE, Winblad B (1981) Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation. J Neural Transm 51: 185–203Google Scholar
  9. Candy JM, Gascoigne AD, Biggins JA (1985) Somatostatin immunoreactivity in cortical and some subcortical regions in Alzheimer's disease. J Neurol Sci 71: 315–323Google Scholar
  10. Carlsson A, Winblad B (1976) Influence of age and time interval between death and autopsy on dopamine and 3-methyoxytyramine levels in human basal ganglia. J Neural Transm 38: 271–276Google Scholar
  11. 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, Calne DB, Lieberman AN, Thorner MD (eds) Ergot compounds and brain function: neuroendocrine and neuropsychiatric aspects. Raven Press, New York, pp 295–304Google Scholar
  12. Chan-Palay V, Asan E (1989) Quantitation of catecholaminergic neurons in the locus cœruleus in human brains of normal young and older adults and in depression. J Comp Neurol 287: 357–372Google Scholar
  13. Cheetham SC, Crompton MR, Czudek C, Horton RW, Katona CLE, Reynolds GP (1989) Serotonin concentrations in brains of depressed suicides. Brain Res 502: 332–340Google Scholar
  14. Cochran E, Robins E, Grote S (1976) Regional serotonin levels in brain: a comparison of depressive suicides and alcoholic suicides. Biol Psychiatry 11: 283–294Google Scholar
  15. Dawbarn D, Hunt SP, Emson PC (1984) Neuropeptide Y: regional distribution, Chromatographic characterization and immunohistochamical demonstration in postmortem human brain. Brain Res 296: 168–173Google Scholar
  16. DeSouza EB, Whitehouse PJ, Kuhar MJ, Price DL, Vale WW (1986) Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. Nature 319: 593–595Google Scholar
  17. Edvinsson L, Ekman R, Thulin T (1991) Increased plasma levels of neuropeptide Y-like immunoreactivity and catecholamines in severe hypertension remain after treatment to normotension in man. Regul Pept 32: 279–287Google Scholar
  18. Ekman R, Wahlestedt C, Böttcher G, Sundler F, Håkanson R, Panula P (1986) Peptide YY-like immunoreactivity in the central nervous system of the rat. Regul Pept 16: 157–168Google Scholar
  19. Ekman R, Servenius B, Castro MG, Lowry PJ, Cederlund AS, Bergman O, Sjögren HO (1993) Biosynthesis of corticotropin-releasing hormone in human T-lymphocytes. J Neuroimmunol 44: 7–14Google Scholar
  20. Fowler CJ, Wiberg Å, Oreland L, Marcusson J, Winblad B (1980) The effect of age on the activity and molecular properties of human brain monoamine oxidase. J Neural Transm 49: 1–20Google Scholar
  21. Gottfries CG, Roos BE, Winblad B (1974) Determination of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and homovanillic acid in brain tissue from an autopsy material. Acta Psychiatr Scand 50: 496–507Google Scholar
  22. Gottfries CG, Adolfsson R, Oreland L, Roos BE, Winblad B (1979) Monoamines and their metabolites and monoamine oxidase activity related to age and to some dementia disorders. In: Cooks J, Stevenson IH (eds) Drugs and the elderly. Perspectives in geriatric clinical pharmacology. MacMillan Press, London, pp 189–197Google Scholar
  23. Harrington MA, Zhong P, Garlow SJ, Ciaranello RD (1992) Molecular biology of serotonin receptors. J Clin Psychiatry 53: 8–27Google Scholar
  24. Herregodts P, Michotte Y, Ebinger G (1989) Regional differences in the distribution of norepinephrine and epinephrine in human cerebral cortex: a neurochemical study using HPLC and electrochemical detection. Neurosci Lett 98: 321–326Google Scholar
  25. Herregodts P, Ebinger G, Michotte Y (1991) Distribution of monoamines in human brain: evidence for neurochemical heterogeneity in subcortical as well as in cortical areas. Brain Res 542: 300–306Google Scholar
  26. Hökfelt T, Johansson O, Ljungdahl A, Lundberg JM, Schultzberg M (1980) Peptidergic neurons. Nature 248: 515–521Google Scholar
  27. Hökfelt T, Lundberg JM, Lagercrantz H (1983) Ocurrence of neuropeptide Y (NPY)-like immunoreactivity in catecholamine neurons in the human medula oblongata. Neurosci Lett 36: 217–222Google Scholar
  28. Joyce D (1962) Changes in the 5-hydroxytryptamine content of rat, rabbit, and human brain after death. Br J Pharmacol 18: 370–380Google Scholar
  29. Korpi ER, Kleinman JE, Goodman SI (1986) Serotonin and 5-hydroxyindoleacetic acid in brains of suicide victims: comparison in chronic schizophrenic patients with suicide as cause of death. Arch Gen Psychiatry 43: 594–600Google Scholar
  30. Kupfermann I (1991) Hypothalamus and limbic system: motivation. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of neural science. Prentice-Hall International Inc, Connecticut, pp 750–760Google Scholar
  31. Leibowitz SF (1986) Brain monoamines and peptides: role in the control of eating behavior. Fed Proc 45: 1396–1403Google Scholar
  32. Leibowitz SF (1989) Hypothalamic neuropeptide Y and galanin: functional studies of coexistence with monoamines. In: Mutt V, Hökfelt T, Fuxe K, Lundberg JM (eds) Neuropeptide Y. Raven Press, New York, pp 267–281Google Scholar
  33. Leibowitz SF (1991) Brain neuropeptide Y: and integrator of endocrine, metabolic and behavioral processes. Brain Res Bull 27: 333–337Google Scholar
  34. Lekman A, Witt-Engerström I, Gottfries J, Hagberg BA, Percy AK, Svennerholm L (1989) Rett syndrome: biogenic amines and metabolites in postmortem brain. Pediatr Neurol 5: 357–362Google Scholar
  35. Leonard BE (1992) Sub-types of serotonin receptors: biochemical changes and pharmacological consequences. Int Clin Psychopharmacol 7: 13–21Google Scholar
  36. Lloyd KG, Farley IJ, Deck JHN (1974) Serotonin and 5-hydroxyindoleacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharmacol 2: 387–397Google Scholar
  37. Martin GR, Humphrey PPA (1994) Receptors for 5-hydroxytryptamine: current perpectives on classification and nomenclature. Neuropharmacology 33: 261–273Google Scholar
  38. McDonald JK, Koenig JI (1993) Neuropeptide Y actions on reproductive and endocrine functions. In: Colmers WF, Wahlestedt C (eds) The biology of neuropeptide Y and related peptides. Humana Press Inc, Totowa, pp 419–456Google Scholar
  39. McEntee WJ, Crook TH (1991) Serotonin, memory and the aging brain. Psychopharmacology 103: 143–149Google Scholar
  40. McGeer EG, Fibiger HC, McGeer PL, Wickson V (1971) Aging and brain enzymes. Exp Gerontol 6: 391–396Google Scholar
  41. McGeer PL, McGeer EG, Suzuki JS (1977) Aging and extrapyramidal function. Arch Neurol 34: 33–35Google Scholar
  42. McIntyre IM, Stanley M (1984) Postmortem and regional changes of serotonin, 5-hydroxyindoleacetic acid, and tryptophan in brain. J Neurochem 42: 1588–1592Google Scholar
  43. McKay 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: 827–839Google Scholar
  44. McLean PD (1955) The limbic system (“visceral brain”) and emotional behaviour. Arch Neurol Psychiatry 73: 130–134Google Scholar
  45. Morgan DG, May PC (1990) Age-related changes in synaptic neurochemistry. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging. Academic Press, New York, pp 219–254Google Scholar
  46. Morley JE, Flood JF (1990) Neuropeptide Y and memory processing. Ann NY Acad Sci 611: 226–231Google Scholar
  47. Nemeroff CB (1991) Corticotropin-releasing factor. In: Nemeroff CB (ed) Neuropeptides and psychiatric disorders. American Psychiatric Press, Washington, pp 77–93Google Scholar
  48. Ohmori T, Arora R, Meltzer H (1992) Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA and tryptophan in frontal cortex of suicide victims. Biol Psychiatry 32: 57–71Google Scholar
  49. Palmer AM, Lowe SL, Francis PT, Bowen DM (1988) Are biochemical studies of postmortem human brain worthwhile? Biochem Soc Trans 16: 472–475Google Scholar
  50. Pare CMB, Young DPH, Price K, Stacey RS (1969) 5-Hydroxytryptamine, noradrenaline and dopamine in brainstem, hypothalamus and caudate nucleus of controls and patients comitting suicide by coalgas poisoning. Lancet i: 133–135Google Scholar
  51. Parsons B, Roxas A, Huang Y-Y, Dwork A, Stanley M (1992) Regional studies of serotonin and dopamine metabolism and quantification of serotonin uptake sites in human cerebral cortex. J Neural Transm [GenSect] 87: 63–75Google Scholar
  52. Perry EK, Blessed G, Tomlinson BE (1981) Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. Neurobiol Aging 2: 251–256Google Scholar
  53. Robinson DS (1975) Changes in monoamine oxidase and monoamines with human developing and aging. Fed Proc 34: 103–107Google Scholar
  54. Robinson DS, Sourkes TL, Nies A, Harris LS, Spector S, Bartlett DL, Kaye IS (1977) Monoamine metabolism in human brain. Arch Gen Psychiatry 34: 89–92Google Scholar
  55. Rubinow DR, Post RM, Davis CL (1991) Somatostain. In: Nemeroff CB (ed) Neuropeptides and psychiatric disorders. American Psychiatric Press, Washington, pp 29–50Google Scholar
  56. Severson J, Marcusson J, Osterburg H, Finch C, Winblad B (1985) Elevated density of [3H]imipramine binding in aged human brain. J Neurochem 45: 1382–1389Google Scholar
  57. Sherif F, Marcusson J, Oreland L (1991) Brain gamma-aminobutyrate transaminase and monoamine oxidase activities in suicide victims. Eur Arch Psychiatry Clin Neurosci 241: 139–144Google Scholar
  58. Schettini G (1991) Brain somatostatin: receptor-coupled transducing mechanisms and role in cognitive functions. Pharmacol Res 23: 203–213Google Scholar
  59. Sloviter RS, Connor JD (1977) Postmortem stability of norepinephrine, dopamine and serotonin in rat brain. J Neurochem 28: 1129–1131Google Scholar
  60. Stallone D, Stunkard AJ (1991) The regulation of body weight: evidence and clinical implications. Ann Behav Med 13: 220–230Google Scholar
  61. Stanley M, Mann JJ, Cohen LS (1986) Serotonin and serotonergic receptors in suicide. Ann NY Acad Sci 487: 122–127Google Scholar
  62. Terry RD, DeTeresa R, Hansen LA (1987) Neocortical cell counts in normal human adult aging. Ann Neurol 21: 530–539Google Scholar
  63. Vijayashankar N, Brody H (1979) A quantitative study of the pigmented neurons in the nuclei locus cœruleus and subcœruleus in man as related to aging. J Neuropathol Exp Neurol 37: 490–497Google Scholar
  64. Wahlestedt C, Ekman R, Widerlöv E (1989) Neuropeptide Y (NPY) and the central nervous system: distribution effects and possible relationship to neurological and psychiatric disorder. Prog Neuropsychopharmacol Biol Psychiatry 13: 31–54Google Scholar
  65. Wallengren J, Ekman R, Sundler F (1987) Ocurrence and distribution of neuropeptides in the human skin. Acta Derm Venereol 67: 185–192Google Scholar
  66. Wester P, Hardy JA, Marcusson J, Nyberg P, Winblad B (1984) Serotonin concentrations in normal aging human brains: relation to serotonin receptors. Neurobiol Aging 5: 199–203Google Scholar
  67. Wester P, Gottfries J, Winblad B (1987) Simultaneous liquid Chromatographic determination of seventeen of the major monoamine neurotransmitters, precursors and metabolites. II. Assessment of human brain and cerebrospinal fluid concentrations. J Chromatogr 415: 275–288Google Scholar
  68. Widdowson PS, Ordway GA, Halaris AE (1992) Reduced neuropeptide Y concentrations in suicide brain. J Neurochem 59: 73–80Google Scholar
  69. Winblad B, Hardy J, Backman L, Nilsson LG (1985) Memory function and brain biochemistry in normal aging and senile dementia. Ann NY Acad Sci 444: 255–268Google Scholar
  70. Wolf WA, Kuhn DM (1983) Simultaneous determination of 5-hydroxytryptamine, its amino acid precursors and acid metabolite in discrete brain regions by high performance liquid chromatography with fluorescence detection. J Chromatogr 275: 1Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • B. Arranz
    • 1
    • 2
  • K. Blennow
    • 3
  • R. Ekman
    • 3
  • A. Eriksson
    • 4
  • J. -E. Månsson
    • 3
  • J. Marcusson
    • 1
  1. 1.Department of Geriatric MedicineUniversity of LinköpingSweden
  2. 2.Departments of Pharmacology and PsychiatryInstitut Municipal d'Investigació MèdicaBarcelonaSpain
  3. 3.Department of Clinical Neuroscience, Section of NeurochemistryUniversity of Göteborg, Mölndal HospitalSweden
  4. 4.Department of Forensic MedicineUniversity of UmeåSweden

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