Elsevier

Neurobiology of Aging

Volume 18, Issue 4, July–August 1997, Pages 431-435
Neurobiology of Aging

Articles
Age-Related Increases in Brain Monoamine Oxidase B in Living Healthy Human Subjects

https://doi.org/10.1016/S0197-4580(97)00037-7Get rights and content

Abstract

Several studies of human brain postmortem report that monoamine oxidase B (MAO B) increases with age and it has been proposed that this increase reflects age-associated increases in glial cells. We measured brain MAO B in a group of normal healthy human subjects (n = 21; age range 23–86; 9 females and 12 males; nonsmokers) using [11C]l-deprenyl-D2 and positron emission tomography. Brain glucose metabolism was also measured with 18FDG in 15 of the subjects. MAO B increased (p < 0.004) in all brain regions examined except the cingulate gyrus. In contrast, subjects showed the expected regional age-related decreases in blood flow and metabolism. In the 15 subjects in whom both MAO B and LCMRglu was measured, there was a trend (p < 0.03) toward an inverse association between brain glucose metabolism and MAO B activity in the frontal and parietal cortices. Although the age-related increase in brain MAO B in living subjects is consistent with postmortem reports, the degree of increase is generally lower.

Section snippets

Subjects

A total of 21 normal subjects, ages 23–86 (average age: 51.3 ± 19.4 years; nonsmokers; 12 men and 9 women) were recruited for this study. Exclusion criteria included history of neurological or psychiatric disorder; head trauma with loss of consciousness; alcohol or substance abuse (except for caffeine and nicotine) and medical conditions that may alter cerebral functioning. Prescan tests ensured the absence of any psychoactive drug use and most of the subjects (15 of 21) received a

Results

The model term λk3, which is a function of MAO B concentration showed a significant increase with age (p < 0.004) in all brain regions examined except for the cingulate gyrus (with a trend for the parietal cortex). Correlation coefficients for brain regions with significant increases with age (p < 0.01) were positive and ranged from 0.60 to 0.74. The results of correlation analysis are shown in Table 1 and individual values for the frontal cortex are shown in Fig. 1A. The same patterns

Discussion

The main findings from this PET study in healthy subjects are that brain MAO B increases with age in all regions examined (except the cingulate gyrus) and that age-related increases in MAO B in living subjects are small relative to those reported for postmortem studies. For example, the whole brain and the cortical regions and the basal ganglia, thalamus, pons and cerebellum showed an average increase of 7.1 ± 1.3%/decade (Table 2) over the age range 23 to 86 years. The frontal cortex showed an

Acknowledgements

This work was supported by Brookhaven National Laboratory (BNL) under contract DE-AC02-76CH00016 with the U.S. Department of Energy and supported by its Office of Health and Environmental Research and by National Institutes of Health Grant NS 15380. The authors thank Alfred Wolf, Richard Ferrieri, David Schlyer, Robert Carciello, Donald Warner, Thomas Martin, Noelwah Netusil, Carol Redvanly, Payton King, Ivana Zezulkova and Lois Caligiuri for their advice and assistance in various parts of this

References (34)

  • A. Carlsson

    Brain neurotransmitters in aging and dementia

    Gerontology

    (1987)
  • G. Cohen

    Monoamine oxidase and oxidative stress at dopaminergic synapses

    J. Neural. Transm. Suppl.

    (1990)
  • C.J. Fowler et al.

    The effect of age on the activity and molecular properties of human brain monoamine oxidase

    J. Neural. Transm.

    (1980)
  • J.S. Fowler et al.

    Inhibition of monoamine oxidase B in the brains of smokers

    Nature

    (1996)
  • J.S. Fowler et al.

    Selective reduction of radiotracer trapping in brain by deuterium substitutioncomparison of [11C]l-deprenyl and [11C]l-deprenyl-D2 for MAO B mapping in human brain

    J. Nucl. Med.

    (1995)
  • J.S. Fowler et al.

    Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson’s diseasethe degree and reversibility of human brain MAO B inhibition by Ro 19 6327

    Neurology

    (1993)
  • M.D. Galva et al.

    Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex

    J. Neural. Transm. [Gen. Sect.]

    (1995)
  • Cited by (216)

    • Age-associated alterations of brain mitochondria energetics

      2023, Biochemical and Biophysical Research Communications
    • The inhibition of monoamine oxidase by 2H-1,4-benzothiazin-3(4H)-ones

      2022, Bioorganic and Medicinal Chemistry Letters
    • Monoamine oxidase inhibitors: A concise review with special emphasis on structure activity relationship studies

      2022, European Journal of Medicinal Chemistry
      Citation Excerpt :

      The activity of MAO-B in CNS increases with age (animals and humans) and growth of glial cells occurs which is responsible for the loss of neurons. Rise in MAO-B transcriptional proteins majorly in Alzheimer disease brain (plaque related astrocytes) is responsible for the higher concentration of MAO-B in brain [48–50]. Functions of brain such as emotions and neurotransmission are managed by the continuous degradation of brain monoamines (dopamine, noradrenaline and 5-hydroxytryptamine).

    • Isatoic anhydrides as novel inhibitors of monoamine oxidase

      2022, Bioorganic and Medicinal Chemistry
    View all citing articles on Scopus
    View full text