Åsa Wiberg

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

The effect of age upon monoamine oxidase -A and -B (MAO-A and -B) in 23 different regions of human brain was determined. There was a significant positive correlation with age in 19 out of 23 regions for MAO-B, but no positive correlation with age was found for MAO-A. The increased MAO-B activity was found, in 5 out of 5 regions tested, to be due entirely to an increased enzyme concentration, rather than due to an increased molecular turnover number of the enzyme. The responses of the mitochondrial marker enzymes succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were studied in 5 brain regions, and no consistent change in activity found with age. The lysosomal enzyme acid phosphatase was found to tend towards an increased activity with age. No difference in either the specific activities or molecular characteristics of MAO were found between men and women. Cross-correlation studies of the data, after compensation for the effects of age, indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain. Such a finding is consistent with a genetic regulation of the enzyme forms.

Biochemical changes in Dementia disorders of Alzheimer type (AD/SDAT)

In postmortem investigations of patients with dementia of Alzheimer type (AD/SDAT) (n = 14) the brain weight was significantly reduced when compared to controls (n = 16). In four AD/SDAT-brain parts investigated the concentrations of 5-hydroxy-tryptamine and noradrenaline were significantly reduced while 3-methoxy-4-hydroxyphenylglycol was significantly increased. In the caudate nucleus of the AD/SDAT-brains the concentrations of dopamine and homovanillic acid were significantly reduced. The activity of monoamine oxidase B was increased suggesting a proliferation of extra neuronal tissue in the AD/SDAT-brains. The activity of choline acetyl transferase was reduced in the four brain parts investigated, showing a general reduction in the acetylcholine system in the AD/SDAT-brains. The ganglioside concentration was significantly reduced suggesting a reduced density of nerve endings in the demented brains. The AD/SDAT-group was according to rating scales severely demented. Patients with an early onset of the dementia disease were more severely intellectually reduced and had more pronounced biochemical disturbances than those with a late onset of the dementia.

Platelet MAO activity and monoamine metabolites in cerebrospinal fluid in depressed and suicidal patients and in healthy controls

Platelet monoamine oxidase (MAO) activity and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were simultaneously measured in 20 currently depressed patients, 11 recovered depressed patients, 15 nondepressed suicide attempters, and 42 healthy control subjects. Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups. Suicide attempters had significantly lower CSF 5HIAA than nonsuicidal patients.

Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type

Abstract Two groups of patients with dementia of Alzheimer type were studied with respect to monoamine oxidase (MAO) activity. In one group of 11 patients MAO activity was determined in platelets and in the other group of 14 patients in the brain (hypothalamus, caudate nucleus, hippocampus and cortex gyrus cinguli) post mortem. The results were compared to controls matched for age and sex. Platelet MAO activity was significantly higher in patients with dementia of Alzheimer type compared to controls. Brain MAO-B activity but not MAO-A activity was significantly higher in the dementia group in hyppocampus and cortex gyrus cinguli. In the controls there were positive correlations for MAO-B activity with age in the four brain regions, but these correlations were absent in the dementia group. This could be explained by differences in age of onset of dementia and that the disease process does not develop homogeneously in different brains.

LOWERED MONOAMINE OXIDASE ACTIVITY IN BRAINS FROM ALCOHOLIC SUICIDES

—Monoamine oxidase (MAO) activity in the brains of 15 suicides, of whom 8 were alcoholics, was compared to a control material of 20 individuals without known mental disorder. At autopsy 13 different parts of the brain were macroscopicaily dissected out and the MAO activity in the samples estimated with β‐phenylethylamine and tryptamine as substrates.

The activity of monoamine oxidase -A and -B in brains from chronic alcoholics

The activity of monoamine oxidase-A was found to be lower in homogenates of hypothalamus and caudate nucleus, but not in cortex of the gyrus cinguli and hippocampus, from chronic alcoholics with respect to homogenates from autopsy cases without histories of alcohol abuse. The activity of monoamine oxidase -B was also lower in the alcoholics, but this could be due to the selective effect of age upon this enzyme form, since the alcoholics were younger than controls. No difference was found for either monoamine oxidase -A or -B activities in brain homogenates from an alcohol preferring (AA) strain of rats, with respect to those from a water preferring (ANA) strain.

Monoamine oxidase activity and kinetic properties in platelet-rich plasma from controls, chronic alcoholics, and patients with nonalcoholic liver disease

The activity of platelet monoamine oxidase was found to be lower in latelet-rich plasma from alcoholics than from controls. This was found for both males and females, and for all three substrates tested (tyramine, tryptamine, and β-phenethylamine). This lower monoamine oxidase activity was not due to liver damage produced by chronic alcoholism, since patients with chronic nonalcoholic liver disease showed an increased platelet monoamine oxidase activity with respect to controls. Furthermore, there was no significant change in the monoamine oxidase activity for the alcoholics after 3 weeks of abstinence, although there was a significant improvement in the livers as measured by a variety of plasma tests for liver damage. The Km value of the monoamine oxidase toward tryptamine was the same for controls, alcoholics, and patients with liver disease.

The activities of monoamine oxidase-A and -B, succinate dehydrogenase and acid phosphatase in the rat brain after hemitransection.

SummaryThe activities of monoamine oxidase-A and-B were determined in four brain regions (limbic system, occipitotemporal cortex, hemispheres and striatum) of the rat 0, 3, 6, 9 and 14 days after hemitransection of the left side. No larger or consistent change in the activity of monoamine oxidase-A towards 5-hydroxytryptamine was found for the left (hemitransected) side with respect to the right side for any of the rats. The monoamine oxidase-B activity towards β-phenethylamine increased in the left side striatum to a significant level by 3 days, and in the hemispheres and occipito-temporal cortex on the left side, with respect to the right side by 9 days, but no significant changes were found for the limbic system. A small decrease in the activity of succinate dehydrogenase was found in the striatum on the left side by 9 days after hemitransection, but no change in the activity of acid phosphatase was found in this brain region.

MONOAMINE OXIDASE ACTIVITY IN PLATELETS AS RELATED TO MONOAMINE OXIDASE ACTIVITY AND MONOAMINERGIC FUNCTION IN THE BRAIN

ABSTRACT In this review the evidence for a correlation between platelet monoamine oxidase and brain monoaminergic function is discussed. It is suggested that platelet monoamine oxidase is genetically determined by the same set of genes that regulate the levels of serotonin turnover in the central nervous system. As a consequence the estimation of platelet monoamine oxidase provides a simple and effective method for the identification of patients at risk for vulnerability to psychiatric illness.

Titration of human brain type-B monoamine oxidase.

The interaction of the substrate-selective irreversible inhibitor J-508 [N-methyl-N-propargyl-(1-indanyl)-ammonium hydrochloride] with the B form of human brain monoamine oxidase has been investigated, and the conditions necessary for this inhibitor to “titrate” the concentration of this enzyme form determined. It was found that the concentration of monoamine oxidase-B determined in this way was the same when either benzylamine or β-phenethylamine was used to assay for activity, which would indicate that this enzyme form is not heterogeneous. Furthermore, the variation in activity from sample to sample was found to be due to a variation in the concentration of available monoamine oxidase-B active centers, rather than due to a variation in the molecular turnover numbers of this enzyme form towards its amine substrates.