Disease relevance of Maoa

• The MAO A/B KO mice showed reduced body weight compared with wild type mice [1].
• This information about the role of MAO-A in the bioactivation of 2'Me-MPTP may be of relevance to those who speculate that the MAO-B catalyzed bioactivation of MPTP or a similar compound may be the cause of idiopathic Parkinson's disease [2].
• Activities of monoamine oxidases, MAOA and MAOB, were measured using radiometric assays in different brain regions of the sparse-fur (spf/Y) mouse, a model of congenital hyperammonemia resulting from an X-chromosomal defect of ornithine transcarbamylase [3].
• The influence of hypoxia (asphyctic and haemic) on MAO-A and MAO-B activity was also investigated [4].
• In contrast, 2'-CH2F-MPTP was oxidized by both MAO-A and MAO-B, and its toxicity was not blocked by pargyline, clorgyline or deprenyl when given separately, but required clorgyline and deprenyl together [5].

Psychiatry related information on Maoa

• Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice: role of a serotonin excess during the critical period [6].
• The female MAOA-deficient mice also displayed normal species-typical maternal behaviors (nesting, nursing, and pup retrieval) [7].
• The MAOA-deficient mice exhibited significantly enhanced classical fear conditioning (freezing to both tone and contextual stimuli) and step-down inhibitory avoidance learning [7].
• MAO A knockout mice differed from C3H mice by attenuated response to restraint (60 min), cold (4 degrees C, 60 min), and water deprivation (48 h) as well as to a chronic (15 days) variable stress [8].
• Age-matched, male Maoa-knockout (KO) mice and wild-type (WT) littermates were tested for nicotine-induced conditioned place preference (CPP); voluntary oral nicotine preference/intake; spontaneous locomotor activity in a novel, inescapable open field; and novelty place preference [9].

High impact information on Maoa

• We examined allele-specific expression of the X-linked monoamine oxidase type A (MAOA) gene and the expression of nine additional X-linked genes in nine cloned XX calves [10].
• MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A [11].
• MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene [11].
• We now report that pargyline, nialamide and tranylcypromine, which inhibit both MAO-A and MAO-B, when administered to mice before MPTP, protect against MPTP-induced dopaminergic neurotoxicity [12].
• Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA [13].

Chemical compound and disease context of Maoa

• These results indicate that both MAO A and MAO B need to be inhibited to increase pethidine toxicity and brain 5-HT levels [14].
• The present results also indicate the importance of the methyl group to selective MAO-A inhibition by the substrate-analogues tested, and the concomitantly induced animal behavior [15].
• Inhibition of MAO B, but not MAO A, blocks DSP-4 toxicity on central NE neurons [16].
• Pretreatment with the selective MAO A inhibitor, clorgyline, had no effect on central NE DSP-4 toxicity [16].
• The effects of clorgyline, the MAO-A inhibitor, and lazabemide, the MAO-B inhibitor, on the levels of the hydroxyl radicals appearing in the cerebral ventricles of mice during brain ischemia/reperfusion were examined by using a salicylate trapping method [17].

Biological context of Maoa

• Observed chase/escape and anxiety-like behavior in the MAO A/B KO mice, different from MAO A or B single KO mice, suggest that varying monoamine levels result in both a unique biochemical and behavioral phenotype [1].
• A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior [1].
• This mutation caused a nonsense-mediated mRNA decay and resulted in the absence of MAO A transcript, protein, and catalytic activity and abrogates a DraI restriction site [1].
• Autoradiographical distribution of imidazoline binding sites in monoamine oxidase A deficient mice [18].
• As previously suggested to explain the raphe autoreceptor loss in 2-month-old MAO-A KO mice, the overall 5-HT1AR down-regulation in mutant pups probably results from extracellular 5-HT excess in both raphe and target structures [19].

Anatomical context of Maoa

• (4) MAOA- and MAOB-expressing neurons are also detected in structures that do not contain aminergic neurons, such as the thalamus, hippocampus, and claustrum [20].
• (3) MAOA is transiently expressed in the cholinergic motor nuclei of the hindbrain, and MAOB is expressed in the forebrain cholinergic neurons [20].
• MAOA is expressed in all noradrenergic and adrenergic neurons early on, and in several dopaminergic cell groups such as the substantia nigra [20].
• Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates [19].
• MAOA activities were decreased in cerebellum (by 23%, P < 0.05) and brainstem (by 16%, P < 0.05) of spf mice; activities of MAOB were concomitantly increased in cerebellum (by 22%, P < 0.05), brainstem (by 20%, P < 0.05) and cerebral cortex (by 22%, P < 0.05) [3].

Associations of Maoa with chemical compounds

• Brain levels of serotonin, norepinephrine, dopamine, and phenylethylamine increased, and serotonin metabolite 5-hydroxyindoleacetic acid levels decreased, to a much greater degree than in either MAO A or B single KO mice [1].
• A reduction in binding to the I(2)-BS, as labelled by both [(3)H]idazoxan and [(3)H]2-BFI (2-(2-benzofuranyl)-2-imidazoline), was seen in the MAO-A knockout animals in both brain and kidney sections, whereas binding to the I(1)-BS in kidney sections remained unchanged [18].
• Data are discussed with reference to the ectopic 5-HT uptake and accumulation reported to occur during the first 10 postnatal days in wild-type and MAO-A KO mice [19].
• The selectivity of the separate assays is further enhanced by the use of inhibitors, deprenyl to block MAO-B and clorgyline to block MAO-A [21].
• Deficiency in the monoamine degradation enzyme monoamine oxidase A (MAOA) or prenatal exposure to the monoamine uptake inhibitor cocaine alters behavior in humans and rodents, but the mechanisms are unclear [22].

Regulatory relationships of Maoa

• Modulation of tyrosine hydroxylase and aromatic L-amino acid decarboxylase after inhibiting monoamine oxidase-A [23].
• Monoamine oxidase-B activity in the forebrain of olfactory bulbectomized mice was higher than that in controls while monoamine oxidase-A activities were unchanged [24].

Other interactions of Maoa

• The binding of [(3)H]Ro19-6327 to MAO-B was unaffected, indicating no change in this isoform in response to the loss of MAO-A [18].
• 5-HT1AR binding was then analyzed in four MAO-A mutant vs. five wild-type neonatal brains, from olfactory bulb to cervical cord [19].
• The anx mutation was correlated with decreased MAOA mRNA in the LC (but not RN), decreased 5HTT mRNA in the RN, and a trend towards lower NET mRNA in the LC [25].
• Elevated levels of aggression have been reported in mice lacking the monoamine oxidase A and the 5-HT1B receptor genes [26].
• This study suggested that the 5-HT circadian rhythm is regulated by TPH and AANAT but not the MAO A gene in this cell line [27].

Analytical, diagnostic and therapeutic context of Maoa

• We have combined in situ hybridization and histochemistry to localize MAOA and MAOB in the developing nervous system of mice [20].
• Rapid and simultaneous determination of monoamine oxidase A and monoamine oxidase B activities in mouse brain homogenates by liquid chromatography with electrochemical detection [21].
• Unlike that seen after treatment with other MAO-A and -B inhibitors, recovery of striatal and hippocampal MAO-A and -B activities from inhibition by TV3326 did not show first-order kinetics [28].
• The distribution of MAO-A and -B in brain and peripheral tissues of Bl/C57 mice and their changes during ageing were studied by quantitative enzyme radioautography with [3H]Ro41-1049 and [3H]Ro19-6327 [29].
• This finding was supported by Northern blot analysis in which MAO A, but not MAO B, transcript was detectable [27].

References