Changes In Monoamine Oxidase Activity Research Articles

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions

Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders.

In vitro and in vivo effect of BU99006 (5-isothiocyanato-2-benzofuranyl-2-imidazoline) on I 2 binding in relation to MAO: Evidence for two distinct I 2 binding sites

BU99006 is an irreversible I 2 ligand which selectively inactivates I 2 binding sites, making it an ideal tool with which to study I 2 site mechanism. We sought to determine the effects of BU99006 on I 2 binding in relation to monoamine oxidase (MAO), and the time course of these effects. In vitro, rat brain membranes that were pre-treated with 10 μM BU99006 showed no change in MAO activity, despite suffering a significant reduction in [ 3H]2BFI binding (52.5 ± 19.6 to 8.5 ± 3.8 fmol mg −1, 84%). Furthermore, reversible I 2 ligands 2BFI and BU224 were able to inhibit MAO, whether treated with BU99006 or not. In vivo, a 5 mg kg −1 i.v. dose of BU99006 in rats rapidly reduced [ 3H]2BFI binding with similar magnitude (85%, maximal reduction after 20 min), without effect on either MAO activity or the specific binding of selective MAO-A and MAO-B radioligands. Moreover, following this irreversible treatment, recovery of central [ 3H]2BFI binding occurred with a rapid half-life of 4.3 h in rat brain (2.0 h in mouse), which is not consistent with a site on MAO. These data indicate that the high affinity site which is occupied by [ 3H]2BFI and irreversibly binds BU99006, is not the same as that which causes inhibition of MAO, and may point to the existence of another I 2 binding site.

Changes in platelet monoamine oxidase activity, cholesterol levels and hyperactive behaviour in adolescents over a period of three years

Platelet monoamine oxidase (MAO) activity is a peripheral marker of central serotonergic activity, and has been associated with aggressive, impulsive and hyperactive behaviour, alcohol and drug abuse. Central serotonergic activity has also been associated with plasma cholesterol levels. In the present longitudinal investigation in adolescents ( n = 320) changes in platelet MAO activity and in plasma cholesterol levels over three years were measured, and their possible association with changes in aggressive and hyperactive behaviour, smoking, alcohol and drug use was studied. The measures were taken at age 15 and 18 years. Psychological data were obtained from teachers by using the Hyperactivity Scale [B. af Klinteberg, Studies on Sex-related Psychological and Biological Indicators of Psychosocial Vulnerability: A Developmental Perspective, University of Stockholm, Department of Psychology, 1988]. The results of the study show that in most of the tested individuals, platelet MAO activity is a relatively stable measure, however, there was a significant number of subjects with a noticeable change in MAO activity. In subjects with decreased platelet MAO activity, total and HDL cholesterol levels were significantly increased. Also, changes in HDL cholesterol and in platelet MAO activity were inversely associated with changes in the score of Concentration Difficulties. The changes in platelet MAO activity and cholesterol level were not associated with alcohol and drug use among the subjects. This longitudinal analysis provides preliminary evidence that changes in platelet MAO activity and cholesterol, which may reflect changes in central serotonergic activity are associated with attention deficit in adolescents.

Monoamine Oxidase Expression During Development and Aging

Monoamine oxidase (MAO) isoenzymes play a major role in regulating the concentration of several bioactive amines, including serotonin and catecholamines. Both in the nervous system and in peripheral organs, MAOs can potentially modulate all the processes involving these bioactive amines. In the present article, we review some of the most significant articles published so far on changes in MAOs during development and aging. The data available on development refer mainly to the mammal brain at fetal and post-fetal stages. Very little work has been done on studying MAO ontogenesis during early development, that is, at stages prior to organogenesis, and what has been done refers to non-mammal vertebrates such as fish, amphibians and birds. MAO A and MAO B changes have been measured as values of enzymatic activity, as amount of protein or, more rarely, as amount of mRNAs. A knowledge of MAO developmental changes not only provides a basis for the investigation of factors regulating MAO expression, but can also contribute to a better understanding of the possible trophic and/or morphogenetic role of monoaminergic neurotransmitters in the developing brain. Transgenic mice lacking MAO A and rodents treated with MAO inhibitors during gestation have been very useful in this second case. The investigations of changes in MAO A and MAO B during aging in the literature refer mostly to humans, mice and rats. Interest in studies on aging is stimulated, among other things, by the observation that age-related diseases leading to neurodegenerative phenomena could be accompanied by changes in MAO activity.

Histochemical demonstration of monoamine oxidase‐containing neurons and an age‐related increase of the enzyme activity in the mouse brain

Monoamine‐containing neurons are especially rich in monoamine oxidase (MAO) and are clustered mainly within the brainstem and diencephalon. They are known to be affected in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. To investigate the distribution of MAO‐containing neurons and any changes in MAO activity with age, brains of male mice (C3H strain) in various age groups (n= 3–5) were studied histochemically and biochemically. Histochemical measurement of MAO activity (the coupled peroxidation method) clearly visualized the localization of MAO‐containing neurons in the mouse brain, such as locus coeruleus, nucleus centralis superior, nucleus raphe dorsalis, etcetera. The staining intensity (MAO activity) of these neurons, within both somata and neurites, increased with age and was accompanied by a moderate increase in neuropils. The biochemical assay (Kraml's method) revealed an age‐related increase in MAO activity, with an abrupt rise until 3 months of age, followed by a further gradual rise until 32 months of age, the age limit examined. To devise a method that is easily applicable to human tissues, the original histochemical method was modified; perfusion fixation was replaced by immersion fixation of sections for 1 min. The result was almost as good as that obtained by the original method. By this modified method, unfixed brains after decapitation of adult mice were kept at 4°C or −20°C for various time intervals and sequentially observed. The observations demonstrated that when brains were frozen immediately after killing and stored at −20°C for 24 h or longer, or cooled and stored at 4°C for 6 h or less, all proved to be suitable for morphological analysis of changes in MAO‐containing neurons. Therefore, this modified method should be applicable to human materials in such diseases as described above.

Changes in monoamine oxidase activity in rat liver during stress.

Effects of some stresses on monoamine oxidase (MAO) activity in rat liver were investigated. Cold stress decreased MAO-A activity. Immobilization stress (IMMO) significantly decreased both MAO-A and MAO-B activities. The MAO-A/MAO-B ratio of the cold stress was significantly decreased, but IMMO was not significantly decreased. These results suggest that cold stress, but not IMMO may change the proportions of the multiple forms of MAO activity.

Changes in monoamine oxidase activity in mouse brain associated with d-methamphetamine dependence and withdrawal

The long-term effects of d-methamphetamine (MP, 5 mg/kg) on brain mitochondrial monoamine oxidase (MAO) activity were studied in mice given MP intraperitoneally daily for 4 weeks. The MAO activities decreased when serotonin (5-HT) and dopamine (DA) were used as substrates. A marked elevation in MAO activity was seen during MP withdrawal when 5-HT, DA, β-phenylethylamine (β-PEA) and norepinephrine (NE) were used as substrates. The kinetics of MAO showed a significant decrease in K m values, but no significant change in V max values during MP withdrawal, despite the presence of NE. The K m and V max values increased when NE was the substrate. Inhibition of MAO by MP or its metabolites (amphetamine, p-hydroxyamphetamine and p-hydroxymethamphetamine) increased with the use of the following substrates in the order: DA, 5-HT, NE and β-PEA.

Effect of L-DOPA Administration on Islet Monoamine Oxidase Activity and Glucose-Induced Insulin Release in the Mouse

Previous studies have shown that the amine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is rapidly converted to its corresponding amine, dopamine, in islet beta-cells. In the present investigation, we studied the effect of acute L-DOPA administration on islet monoamine oxidase (MAO) activity and on glucose-induced insulin secretory response in mice. It was observed that at 2 min after intravenous L-DOPA administration, there was a marked increase (+35%) in islet MAO activity, with serotonin as substrate. At 7 min, MAO activity towards dopamine was enhanced by 32% and that towards serotonin and phenylethylamine (PEA) was decreased by 23 and 25%, respectively. The inhibitor of L-aromatic amino acid decarboxylase, benserazide, abolished L-DOPA-induced changes of MAO activity, suggesting that the formed dopamine, and not L-DOPA itself, was responsible for the observed effects. At 60 min, no effect by L-DOPA administration on islet MAO activity was noticed. L-DOPA (125 or 250 mumol/kg), given together with glucose, induced a decrease in glucose-induced insulin response. L-DOPA (125 mumol/kg), given 7 min before glucose, totally suppressed glucose-induced insulin response. This inhibition was eliminated through pretreatment with benserazide. Enhancement of glucose-stimulated insulin response, after deposition of horseradish peroxidase (HRP) in beta-cell vacuolar system, was suppressed by L-DOPA. We conclude that acute L-DOPA-induced dopamine accumulation in pancreatic islets is accompanied by rapid changes in MAO activity, concomitant with an inhibitory effect on glucose-stimulated insulin response. Increased hydrogen peroxide production, following increased MAO activity, may possibly augment the inhibitory effect of dopamine accumulation on insulin release.

Relationship of Gonadal Hormone Administration, Sex, Reproductive Status and Age to Monoamine Oxidase Activity Within the Hypothalamus

Abstract Activity of Type A monoamine oxidase (MAO) was measured in microdissected samples from preoptic-hypothalamic and hindbrain areas of young male and female rats, and aged female rats. Administration of estradiol and progesterone, in doses sufficient to facilitate lordosis behavior and induce a luteinizing hormone surge in ovariectomized, but not castrated rats, was associated with sexually dimorphic changes of MAO activity within the hypothalamus. Forty-two h following estradiol benzoate administration, increased MAO activity was measured in the ventromedial nucleus (VML) and midbrain central gray of females, while decreased MAO activity was measured in the VML and arcuate-median eminence (ArME) of males. Progesterone administration to estradiol benzoate-primed rats was associated with decreased MAO activity in the VML and medial preoptic nucleus (mPOA) of females and decreased activity in the dorsal raphe nucleus of males. Activity of MAO on diestrus, proestrus and estrus was assessed in ten preoptic-hypothalamic and hindbrain sites. Differences between days of the cycle were limited to the mPOA, ArME and VML. While activities were generally lowest at estrus, these areas exhibited different patterns of activity across the cycle. Activity was highest at proestrus in the mPOA and highest at diestrus in the VML and ArME. Activity of MAO in some areas of 25-month old, diestrus rats was altered as compared to young, cycling rats; however, ageing was not associated with widespread changes in MAO activity. In the suprachiasmatic nucleus, aged rats showed approximately 30% less activity than young rats. In the mPOA, VML and ArME, activity in aged females was different from some, but not all, days of the estrous cycle. These results show that MAO activity changes within specific hypothalamic sites when the neuroendocrine axis is altered. Since the changes are present in areas where activity of rnonoaminergic systems is critical for initiating gonadotrophin surges and inducing lordosis behavior, these results provide initial evidence that catabolism of monoamines by MAO may contribute to rnonoaminergic regulation of reproductive function.

Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases.

Tetrahydroisoquinoline (TIQ) alkaloids and 1-carboxy TIQ derivatives have been found in human fluids and/or tissues. The possible biosynthetic pathways of salsolinol (Sal), taken as an example of TIQs, are discussed, and the possibility that biosynthesis occurs through a stereospecific enzymatic reaction is considered. In this respect, it is reported that the R enantiomer of Sal predominates in urines of healthy volunteers, whereas the S enantiomer predominates in port wine and possibly in other beverages and foods, suggesting that Sal present in humans could have, at least partially, and endogenous enzymatic origin. TIQs and other dopamine-derived alkaloids are weak MAO inhibitors, the R enantiomer of Sal and salsolidine being more potent than the S form. The changes in monoamine oxidase activity and the nigrostriatal concentrations of dopamine and homovanillic acid in Parkinson's and Huntington's diseases and in alcoholism are reviewed. In these pathological situations, changes in the levels of dopamine-derived alkaloid levels may occur. The possibility that the modifications found might cause or contribute to changes in mental and/or neurophysiological states in these pathological situations is considered.

Changes in monoamine oxidase activity by mitochondria isolated from late embryos of Bufo bufo

1. 1. Monoamine oxidase activity has been assayed in mitochondria isolated from post-neural embryos (stages 14–25) of Bufo bufo, using 5-HT and PEA as substrates. 2. 2. Mitochondria isolated from stages 19 to 25 show an increasing ability in deaminating monoamines, PEA being metabolized at a higher level with respect to 5-HT. 3. 3. At all the examined stages 5-HT is metabolized by an enzyme corresponding to MAO A, while PEA, from stage 19, is largely deaminated by a semicarbazide-sensitive amine oxidase (SSAO). 4. 4. The effect of Triton X-100 on MAO A activity appears remarkably different in mitochondria isolated from embryos at stages 14 and 25 respectively.

Changes in MAO activities in several organs of rats after administration of l-thyroxine.

Male rats were given daily injections of 200 micrograms/kg l-thyroxine, s.c., for a period of 10 days. Monoamine oxidase (MAO) activities in the heart, lung and liver mitochondria decreased rapidly to about 50% those of the control rats with 5-HT and beta-phenylethylamine (beta-PEA) as substrates on the first day. After that, heart MAO activity increased gradually and exceeded the control value after 10 days with 5-HT as the substrate. The level of liver MAO activity was maintained at about 50-70% during the same period of administration with 5-HT as the substrate. The thyroxine treated rats showed no marked change in brain MAO activity. In vitro, l-thyroxine and its metabolites had no discriminative actions on MAO activities in these organs of rats. The heart, lung and liver MAO have unaltered Km values for 5-HT and beta-PEA, but decreases in the Vmax for both substrates were observed between the control and l-thyroxine-treated rats. Addition of the brain, heart and liver cytosol fractions from l-thyroxine treated rats caused MAO activities of heart mitochondria to decrease with 5-HT as a substrate and caused them to increase with beta-PEA as a substrate. MAO activities in liver also were inhibited by adding all the cytosols when beta-PEA was the substrate, but on the contrary, lung MAO activities were increased when 5-HT was the substrate. These results indicate the possible presence of multiple modulators of MAO in the cytosol fractions of l-thyroxine treated rats.

Changes in MAO Activities in Several Organs of Rats after Administration of /-Thyroxine

Male rats were given daily injections of 200 μg/kg /-thyroxine, s.c. for a period of 10 days. Monoamine oxidase (MAO) activities in the heart, lung and liver mitochondria decreased rapidly to about 50% those of the control rats with 5-HT and β-phenylethylamine (β-PEA) as substrates on the first day. After that, heart MAO activity increased gradually and exceeded the control value after 10 days with 5-HT as the substrate. The level of liver MAO activity was maintained at about 50-70% during the same period of administration with 5-HT as the substrate. The thyroxine treated rats showed no marked change in brain MAO activity. In vitro, /-thyroxine and its metabolites had no discriminative actions on MAO activities in these organs of rats. The heart, lung and liver MAO have unaltered Km values for 5-HT and β-PEA but decreases in the Vmax for both substrates were observed between the control and /-thyroxine-treated rats. Addition of the-brain, heart and liver cytosol fractions from /-thyroxine treated rats caused MAO activities of heart mitochondria to decrease with 5-HT as a substrate and caused them to increase with β-PEA as a substrate. MAO activities in liver also were inhibited by adding all the cytosols when β-PEA was the substrate, but on the contrary, lung MAO activities were increased when 5-HT was the substrate. These results indicate the possible presence of multiple modulators of MAO in the cytosol fractions of /-thyroxine treated rats.

Gonadal hormone regulation of MAO and other enzymes in hypothalamic areas.

Activities of type A monoamine oxidase (MAO), acetylcholine esterase (AChE), and glucose-6-phosphate dehydrogenase (G6PDH) were differentially altered in hormone-sensitive areas of the preoptic-hypothalamic continuum after administration of estrogen and progesterone. Estrogen increased activity of AChE in the bed nucleus of the stria terminalis and activity of G6PDH in the periventricular area (PVE) of the preoptic area, arcuate-median eminence (Ar-ME) and pituitary. Estrogen decreased activity of MAO in the PVE of the anterior hypothalamus, pars lateralis of the ventromedial nucleus and in the Ar-ME. Acute administration of progesterone (1 h) to estrogen-treated females did not further alter estrogen-dependent changes in AChE or G6PDH; however, MAO activity in the ventromedial nucleus and Ar-ME was rapidly increased after progesterone. Without prior estrogen administration, progesterone did not affect MAO activity. Administration of the protein synthesis inhibitor anisomycin prior to progesterone did not antagonize progesterone-dependent increases in MAO. Progesterone added in vitro to homogenates from estrogen-treated but not from untreated females increased MAO activity. The hormonal specificity, time course of effects and anatomical location of the enzymatic changes suggest that some of them may participate in the mediation of gonadal hormone action in the CNS. In particular, changes in MAO activity in the ventromedial nucleus and Ar-ME are consistent with reported effects of these hormones on monoamine turnover which in turn have been suggested to contribute to hormonal regulation of feminine sexual behavior and gonadotropin secretion.

Preferential inhibition of the B-form of monoamine oxidase in the liver of rats given 3'-methyl-4-dimethylaminoazobenzene in the diet

A and B-form monoamine oxidase (MAO) activities were measured in the liver of rats maintained with a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). A-form MAO activity was similar to the control value throughout the feeding periods with serotonin as substrate. In contrast, B-form MAO activity decreased rapidly and the level of MAO activity was maintained at about 30% with β-phenylethylamine (β-PEA) as substrate. 3'-Me-DAB feeding did not cause any changes in MAO activity in the brain of rats. A single administration of 3'-Me-DAB (100 mg/kg p.o.) failed to alter A and B-form MAO activities for up to 4 days after its administration. The mechanism of inhibition of B-form MAO activity in rat liver mitochondria by 3'-Me-DAB was investigated. The inhibition of 3'-Me-DAB of B-form MAO activity, in vitro, was competitive and reversible. There was no difference in the apparent Michaelis constant toward β-PEA between control and 3'-Me-DAB fed rats. B-form MAO in rat liver mitochondria was titrated with (−)deprenyl; this compound is selective to and an irreversible inhibitor of B-form MAO. The content of B-form MAO in liver mitochondria of rats fed 3'-Me-DAB for 3 weeks was decreased to about 60% of the control level.

Effects of monoamine oxidase inhibition on female sexual behavior, serotonin levels and type A and B monoamine oxidase activity.

Administration of various monoamine oxidase (MAO) inhibitors to ovariectomized-adrenalectomized, estrogen and progesterone-treated female rats was utilized to study possible relationships between the lordosis response and levels of preoptic-hypothalamic MAO and serotonin (5HT). Depending on the drug and dose, behavioral changes ranged from no effect to complete abolition of the lordosis response. Surprisingly, only those treatments which substantially inhibited both the A and B forms of MAO affected lordosis. However, behavioral deficits were related to increases in 5HT levels in a graded manner. In fact, a sigmoid-shaped dose-response curve was generated by plotting either the lordosis quotient or quality score versus the percent increase in preoptic-hypothalamic 5HT. Proceptivity was reduced by some treatments but not abolished, suggesting that different neurotransmitters may mediate receptive and proceptive components of female sexual behavior. In general, these results support the hypothesis that 5HT may exert inhibitory control over hormone dependent female sexual behavior and suggest that previously reported changes in MAO activity and 5HT levels following gonadal steroid treatment could pay a role in hormonal facilitation of female sexual behavior.

Changes in Monoamine Oxidase Activity in Rat Brain During Alloxan Diabetes

The effect of alloxan diabetes on the activity of monoamine oxidase was studied in three regions of the rat brain at various time intervals after the onset of diabetes. It was observed that monoamine oxidase activity was decreased at early time intervals after diabetes, followed by a recovery in all three regions of the brain. A reversal of the effect was observed with insulin administration to the diabetic rats.

Changes in monoamine oxidase activity associated with the uncoupling of rat liver mitochondria

Changes in monoamine oxidase activity associated with the uncoupling of rat liver mitochondria

The influence of benserazide on changes in monoamine oxidase activity in some rat tissues following treatment with L-DOPA.

1. This study was designed to see whether or not increases in monoamine oxidase (MAO) specific activity that follow chronic treatment of rats with L-dihydroxyphenylalanine (L-DOPA) could be modified by benserazide (Ro 4-4602), an inhibitor of L-aromatic amino acid decarboxylase, and to compare the properties of the increased MAO activity with those of control animals. 2. Male wistar rats were treated with L-DOPA (250 mg/kg) and benserazide (40 mg/kg) either alone or in combination for 10 days. 3. The activity of MAO in homogenates of heart, kidney, liver and brain was measured with 5-hydroxytryptamine (5-HT) and benzylamine (BZ). 4. The significant increases in MAO specific activity seen in heart and kidney following L-DOPA treatment could be reduced or prevented by benserazide. 5. Use of the selective MAO inhibitor clorgyline showed that the increases in MAO specific activity, when measured with either 5-HT or BZ were due to an increase in the number of active centres of MAO-A, in the rat heart. 6. There was a significant increase in the Vmax of the enzyme reaction with 5-HT, in the rat heart and kidney homogenates. 7. It is concluded that L-DOPA increases the specific activity of MAO-A in rat heart and kidney as a result of its decarboxylation.

Prenatal programming of hepatic monoamine oxidase by 5,5-diphenylhydantoin

During ontogeny, rat liver monoamine oxidase gradually increased in activity in both sexes until the pubertal period when female activity rose 1.5- to 2.0-fold higher than male activity. Oral administration of 5,5-diphenylhydantoin (10 mg/kg body wt) to pregnant rats on days 7,9, 12, 14and 16 of gestation had no effect on the monoamine oxidase activity of immature male or female offspring. The enzyme activity in adult male offspring, from females prenatally treated with diphenylhydantoin, was elevated to a level similar to that of adult females. Subcutaneous injection of diphenylhydantoin (10 mg/kg body wt) for 5 days prior to death failed to induce changes in monoamine oxidase activity in either pre- or postpubertal males or females. Thus, prenatal administration of diphenylhydantoin can program changes in adult male monoamine oxidase activity. The serum levels of testosterone in the male offspring of prenatally treated females, on days 5 and 63 postpartum, were the same as those of their respective controls, demonstrating that the changes caused by diphenylhydantoin are not due to diminished levels of testosterone.