Summary
Age-related modifications of monoamine oxidase-A and -B (MAO-A and MAO-B) and amine metabolite concentrations were studied in human frontal cortex taken postmortem from 22 subjects of various ages (21–75 years). Qualitative and quantitative analysis for MAO-B was provided by kinetic studies with a specific radioligand, [3H]lazabemide. The data demonstrated a significant (P < 0.05) positive correlation between the density of [3H]lazabemide binding sites (Bmax) and age of the subject, without showing an apparent modification in the dissociation constant (KD) of the radioligand. In parallel experiments, MAO-B but not MAO-A activity was shown to correlate with age (P < 0.05). The concentrations of the amine metabolites 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) were all devoid of a correlation with age. Neither did the concentrations of these metabolites relate to the respective subject's MAO-B enzymatic activity nor to [3H]lazabemide Bmax. A correlation, though rather weak, was obtained between MAO-A activity and MHPG concentration (P=0.045). The MAO-A and -B enzyme characteristics in subjects who had committed suicide (n=9) did not differ from those of subjects deceased for other causes (n=13). Among the measured monoamine metabolites the concentrations of DOPAC and HVA were higher in the suicide versus control group (P < 0.05). The present data confirm in a direct manner that the increase in MAO-B activity in aging brain is due to an enhancement of the number of active sites of the enzyme and not through modifications of its kinetic characteristics. Furthermore, that neither the characteristics nor the activity of the enzyme are changed in the frontal cortex of suicide victims compared to control subjects.
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Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979) Postmortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and a review of the literature. J Neural Transm 45: 81–105
American Psychiatric Association (1987) DSM-III-R: diagnostic and statistical manual of mental disorders, 3rd ed, revised. American Psychiatric Press, Washington DC
Asberg M, Traskman L, Thorèn P (1976) 5-HIAA in the cerebrospinal fluid-a biochemical suicide predictor? Arch Gen Psychiatry 33: 1193–1197
Bach AWJ, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan S-W, Seeburg PH, Shih JC (1988) DNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 85: 4934–4938
Banki CM, Arato M, Papp Z, Kurcz M (1984) Cerebrospinal fluid amine metabolites and neuroendocrine findings: biochemical markers in suicide patients? J Affect Disord 6: 34–350
Beskow J, Gottfries CG, Roos BE, Winblad B (1976) Determination of monoamine and monoamine metabolites in human brain: post mortem studies in a group of suicides and in a control group. Acta Psychiatr Scand 53: 7–20
Bourne HR, Bunney WR Jr, Colburn RW, Davis JM, Shaw DM, Coppen AJ (1968) Noradrenaline, 5-hydroxytryptamine 5-hydroxyindoleacetic acid in the hindbrains of suicidal patients. Lancet ii: 805–808
Brown GL, Goodwin FK, Ballenger JC, Goyer PK, Major LF (1979) Aggression in humans correlate with cerebrospinal fluid metabolites. Psychiatry Res 1: 131–139
Cao Danh H, Strolin Benedetti M, Dostert P (1984) Differential changes in monoamine oxidase A and B activity in aging rat tissues. In: Tipton KF, Dostert P, Strolin Benedetti M (eds) Monoamine oxidase and disease-Prospects for therapy with reversible inhibitors. Academic Press, London, pp 301–317
Carlsson A, Adolfsson R, Aquilonius S-M, Gottfries C-G, 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 A, Thorner MO (eds) Ergot compounds and brain function: neuroendocrine and neuropsychiatric aspects. Raven Press, New York, pp 295–304
Cawthon RM, Pintar JE, Haseltine FP, Breakefield XO (1981) Differences in the structure of A and B forms of human monoamine oxidase. J Neurochem 37: 363–372
Cesura AM, Galva MD, Imhof R, Da Prada M (1987) Binding of [3H]Ro 16-6491, a reversible inhibitor of monoamine oxidase type B, to human brain mitochondria and platelet membranes. J Neurochem 48: 170–176
Cesura AM, Imhof R, Takacs B, Galva MD, Picotti GB, Da Prada M (1988) [3H]Ro 16-6491, a selective probe for affinity labelling of monoamine oxidase type B in human brain and platelet membranes. J Neurochem 50: 1037–1043
Cesura AM, Galva MD, Imhof R, Kyburz E, Picotti GB, Da Prada M (1989) [3H]Ro 19-6327: a reversible ligand and affinity-labeling probe for monoamine oxidase-B. Eur J Pharmacol 162: 457–65
Cesura AM, Pletscher A (1992) The new generation of monoamine oxidase inhibitors. Prog Drug Res 38: 171–297
Cesura AM, Richards JC, Picotti GB, Kettler R, Imhof R, Da Prada M (1993) Reversible monoamine oxidase inhibitors: from laboratory to clinic. In: Yasuhara H, Parvez SH, Sandler M, Oguchi K, Nagatsu T (eds) Monoamine oxidase: basic and clinical aspects. VSP Press, Utrecht, pp 159–166
Chen ZY, Hotamisligil GS, Huang JK, Wen L, Ezzeddine D, Aydin-Muderrisoglu N, Powell JF, Huang RH, Breakefield XO, Craig I, Hsu Y-PP (1991) Structure of the human gene for monoamine oxidase type A. Nucleic Acid Res 19: 4537–4541
Cochran E, Robins E, Grote S (1976) Regional serotonin levels in brain: a comparison of depressive suicides and alcoholic suicides with controls. Biol Psychiatry 11: 283–294
Da Prada M, Kettler R, Keller HH, Cesura AM, Richards JG, Saura Marti J, Muggli-Maniglio D, Wyss PC, Kyburz E, Imhof R (1990) From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors. J Neural Transm [Suppl 29]: 279–292
Fowler CJ, Wiberg A, 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: 1–20
Fowler CJ, Tipton KF, MacKay AVP, Youdim MBH (1982) Human platelet monoamine oxidase — a useful enzyme in the study of psychiatric disorders? Neuroscience 7: 1577–1594
Fowler CJ, Ross SB (1984) Selective inhibitors of monoamine oxidase A and B: biochemical, pharmacological and clinical properties. Med Res Rev 4: 323–358
Gerlo E, Malfait R (1985) High-performance liquid Chromatographie assay of free norepinephrine, epinephrine, dopamine, vanillylmandelic acid and homovanillic acid. J Chromat 343: 9–20
Gottfries CG, Oreland L, Wiber A, Winblad B (1975) Lowered monoamine oxidase activity in brain from alcoholic suicides. J Neurochem 25: 667–673
Gottfries C-G, von Knorring L, Oreland L (1980) Platelet monoamine oxidase activity in mental disorders-II. Affective psychoses and suicidal behavious. Prog Neuropsychoparmacol 4: 185–192
Gottfries C-G, Adolfsson R, Aquilonius S-M, Carlsson A, Eckernas S-A, Nordberg A, Oreland L, Svennerholm L, Wiberg A, Winblad B (1983) Biochemical changes in dementia disorder of Alzheimer type (AD/SDAT). Neurobiol Aging 4: 261–271
Haefely WE, Kettler R, Keller HH, Da Prada M (1990) Ro 19-6327, a reversible and highly selective monoamine oxidase B inhibitor: a novel tool to explore the MAO-B function in humans. Adv Neurol 53: 505–511
Konradi C, Riederer P, Youdim MB (1986) Hydrogen peroxide enhances the activity of monoamine oxidase type-B but not of type-A: a pilot study. J Neural Transm [Suppl] 22: 61–73
Lloyd KG, Farley IJ, Deck JHN, Hornykiewicz O (1974) Serotonin and 5-hydroxyindoleacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharmacol 11: 387–397
Lowry OH, Rosebrough NF, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275
Mac Kay AVP, Davies P, Dewar AJ, Yates CM (1978) Regional distribution of enzymes associated with neurotrasmission by monoamines, acetylcholine and GABA in the human brain. J Neurochem 30: 827–839
McPherson GA (1985) Analysis of radioligand binding experiments: a collection of computer programs for the IBM PC. J Pharmacol 14: 213–228
Ohmori T, Arora RC, Metzer HY (1992) Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA, and tryptophan in frontal cortex of suicide victims. Biol Psychiatry 32: 57–71
Oreland L, Fowler CJ (1979) The activity of human brain and thrombocyte monoamine oxidase (MAO) in relation to various psychiatric disorders. The nature of the changed MAO activity. In: Singer TP, von Korff RW, Murphy DL (eds) Monoamine oxidase: structure, function and altered functions. Academic Press, New York, pp 389–396
Oreland L, Wiberg A, Asberg M, Traskman L, Sjostrand L, Thoren P, Bertilsson L, Tybring G (1981) Platelet MAO activity and monoamine metabolites in cerebrospinal fluid in depressed and suicidal patients and in healthy controls. Psychiatry Res 4: 21–29
Oreland L, Gottfries C-G (1986) Brain and brain monoamine oxidase in aging and dementia of Alzheimer type. Prog Neuropsychopharmacol Biol Psychiatry 10: 533–540
Palmer AM, Wilcock GK, Esiri MM, Francis PT, Bowen DM (1987) Monoaminergic innervation of the frontal and temporal lobes in Alzheimer's disease. Brain Res 401: 231–238
Robinson DS (1975) Changes in monoamine oxidase and monoamines with human development and aging. Fed Proc 34: 103–107
Roy A, Agren H, Pickar D, Linnoila M, Doran AR, Cutler NR, Paul SM (1986) Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindolacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression. Am J Psychiatry 143: 1539–1545
Sastre M, Garcìa-Sevilla JA (1993) Opposite age-dependent changes of alpha2A-adrenoceptors and nonadrenoceptor [3H]idazoxan binding sites (I2-imidazoline sites) in human brain: strong correlation of I2 with monoamine oxidase-B sites. J Neurochem 61: 881–889
Saura Marti J, Kettler R, Da Prada M, Richards JG (1990) Molecular neuroanatomy of MAO-A and MAO-B. J Neural Transm [Suppl] 32: 49–53
Saura Marti J, Kettler R, Da Prada M, Richards JG (1992) Quantitative enzyme radioautography with3H-Ro 41-1049 and3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. J Neurosci 12: 1977–1999
Simonsson P, Traskman-Bendz L, Ailing C, Oreland L, Regnell G, Ohman R (1991) Peripheral serotonergic markers in patients with suicidal behaviour. Eur Neuropsychopharmacol 1: 503–510
Sparks DL, Woeltz VM, Markesbery WR (1991) Alterations in brain monoamine oxidase activity in aging, Alzheimer's disease, and Pick's disease. Arch Neurol 4: 718–721
Strolin Benedetti M, Keane PE (1980) Differential changes in monoamine oxidase A and B activity in the aging rat brain. J Neurochem 35: 1026–1032
Strolin Benedetti M, Dostert P (1989) Monoamine oxidase, brain aging and degenerative diseases. Biochem Pharmacol 38: 555–561
Strolin Benedetti M, Dostert P (1992) Monoamine oxidase: from physiology and pathophysiology to design and clinical application of reversible inhibitors. Adv Drug Res 23: 65–125
Traskman L, Asberg M, Bertilsson L, Sjostrand L (1981) Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry 38: 631–636
Walsh CT (1984) Suicide substrates, mechanism-based enzyme inactivators: recent developments. Annu Rev Biochem 53: 493–535
Westlund KN, Denney RM, Kochsperger LM, Rose RM, Abell CW (1985) Distinct MAO A and MAO B populations in the primate brain. Science 230: 180–183
Westlund KN, Denney RM, Rose RM, Abell CW (1988) Localisation of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brain stem. Neuroscience 25: 439–456
Wurtman RJ, Axelrod J (1963) A sensitive and specific assay for the estimation of monoamine oxidase. Biochem Pharmacol 12: 1439–1441
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Galva, M.D., Bondiolotti, G.P., Olasmaa, M. et al. Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex. J. Neural Transmission 101, 83–94 (1995). https://doi.org/10.1007/BF01271547
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DOI: https://doi.org/10.1007/BF01271547