Monoamine Oxidase Type A Research Articles

Potencial uso terapêutico da ayahuasca: Uma revisão da literatura

ABSTRACT Ayahuasca is a psychoactive decoction originally used in indigenous Amazonian culture. It consists of a dense brown liquid that most frequently results from the decoction of two plants native to the Amazon rainforest, Psychotria viridis (Rubiaceae) and Banisteriopsis caapi (Malpighiaceae). The composition of the decoction is variable, as several plant species can be used in its preparation. Its psychoactive effect occurs due to the presence of N,N-dimethyltryptamine (DMT), an agonist at serotonergic receptors (5-HT1A/2A/2C) that is metabolized by the enzyme monoamine oxidase type A (MAO-A), and also the presence of β-carbolines, which are reversible MAO-A inhibitors. This joint interaction promotes a sequence of psychedelic neurochemical effects. Due to the current expansion of research on psychedelic substances and the growing public interest in the benefits of ayahuasca beyond its traditional use in the Amazon, academic research on its therapeutic capacity has been increasing. This study aimed to carry out a literature review on the scientific evidence for the therapeutic potential of ingesting ayahuasca. The review covered the period 2012-2022, and resulted in evidence on the therapeutic effects of ayahuasca on depression/anxiety, chemical dependency/alcoholism and Parkinson’s disease, as well as neuropsychological effects, and possible toxic effects on reproduction/embryonic development, among other adverse effects. The highest number of publications in the searched period dealt with the effects of ayahuasca on depression and anxiety. Further studies need to address the detailed mechanism of action of ayahuasca, as well as its potential toxicity, in order to demonstrate its safety.

Water-soluble essential oil components of flowers of Paeonia × suffruticosa cultivars and in silico analysis with antidepressant targets

The present study focused on water-soluble essential oil recovered from the hydrolate of ten Paeonia × suffruticosa cultivars. Thirty-seven components, mostly oxygenated compounds (94.6–99.6%), were detected by gas chromatography–mass spectrometry (GC-MS) and GC–flame ionisation detector (GC-FID). The geranic acid chemotype was discovered (in cultivar ‘Lan BaoShi’). Eight key oxygenated components were analysed in silico with antidepressant targets sodium-dependent serotonin transporter (SERT), 5-hydroxytryptamine receptor 1 A (5-HT1A), and monoamine oxidase type A (MAO-A). Geraniol, nerol, citronellol, and geranic acid presented superior docking properties. Phenylethyl alcohol and 1,3,5-trimethoxybenzene were also well docked. These molecules were bound to the active sites successfully (with partial occupancy in SERT). They might increase serotonin level or mimic its effect in central nervous system. (Z)-3-Hexen-1-ol and 1-hexanol showed weak binding. The in silico analysis revealed for the first time that the key water-soluble essential oil components of P. × suffruticosa potentially targeted antidepressant targets.

The modulation of mRNA levels of MAOA by electroacupuncture and psychotherapy in patients with pathological internet use.

ObjectiveThe aim of this study was to observe the efficacy of electroacupuncture (EA) and psychotherapy (PT) effect on the mental status, sleep quality and impulsive trait in patients with pathological internet use, and to observe the changes of Monoamine oxidase type A (MAOA) messenger Ribonucleic acid (mRNA) levels in each group.MethodsA total of 60 PIU patients were included for the present study. These patients were randomly divided into two groups: EA group and PT group. Baihui, Sishencong, Hegu, Neiguan, Shenmen, Taichong, Sanyinjiao and Xuanzhong were selected for acupuncture in the EA group, while group psychotherapy combined with individual psychotherapy was used for intervention in patients in the PT group. Young’s Internet addiction Test (IAT), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Barratt Impulse Scale (BIS-11) and Pittsburgh Sleep Quality Index (PSQI) were used to observe the severity of Internet addiction, mental status, sleep quality and impulsive trait of all patients at baseline and 40th days of treatment; and MAOA mRNA data were collected at baseline and 40th days of treatment.ResultsElectroacupuncture and psychological intervention effectively reduced IAT, SAS, SDS, Y-BOCS, BIS and PSQI scores of PIU patients. After 40 days treatment, the MAOA expression of the PT group was increased, and there was no significant change in EA group. The correlation analysis indicated that IAT scores were positively correlated with SAS, SDS, Y-BOCS, BIS and PSQI at baseline. In addition, after treatment the EA group showed that the change in IAT scores was positively correlated with the change in Y-BOCS and BIS scores, and the PT group showed that the change in IAT scores was positively correlated with the change in SDS, BIS and PSQI scores.ConclusionThe present study showed that electroacupuncture and psychological intervention can improve severity of Internet addiction, mental status, sleep quality and impulsive trait of PIU patients. Simultaneously, neurobiological changes may be the underlying mechanisms of psychotherapy for internet additcion.

In silico study to identify new monoamine oxidase type a (MAO-A) selective inhibitors from natural source by virtual screening and molecular dynamics simulation

Neurological (such as stroke, Alzheimer's, Parkinson's, epilepsy) and neuropsychiatric (such as autism, migraine, depression, anxiety, stress) disorders continue to be on rising every year with an increase of 20.5% and 13%, respectively. These diseases are critical, life-threatening and in most cases may lead to other precarious human disorders and causing a psychological as well as economic burden on patients and society all over the world that consequently led to a high mortality rate. Notably, Monoamine oxidase (MAO) enzymes are classified as potential drug target for the treatment of such neurological disorders because of their significant role in neurotransmitter degradation that results in the production of certain neurotoxic compounds (such as H2O2, NH3). So far, many MAO inhibitors have been introduced however, the need for a novel potent therapeutic alternative still exists due to significant hypertensive crises, hepatotoxicity and extremely poor selectivity related to nonselective irreversible MAOIs. Therefore, the goal of the current study was to find novel natural compounds that may be used as medicine to treat neurological disorders without causing any harmful side effect. For this purpose, a computational-based virtual screening of 29,000 natural product library (of Natural Product Atlas) from the microbial source is performed through molecular docking and dynamics simulation approach. As a result, about 20 novel potent compounds were successfully shortlisted by implementing molecular docking studies, certain pharmacological, physiological and ADMET properties criteria. Among them, six compounds i.e., NPA000487, 001,637, 007,129, 012,149, 15,149 and NPA0018844 were predicted with a potential to cross BBB and target MAO-A. Furthermore, MD simulations were performed to evaluate the stability and dynamics behavior of these compounds with MAO-A complex for about 50 ns. Eventually, NPA007129, NPA0012149, and NPA0015149 were identified as highly steady complex after 15 ns. Our findings implied that NPA007129, NPA0012149, and NPA0015149 are potential MAO-A inhibitors. Nevertheless, further experimental validation is needed as part of the follow-up investigation.

MRNA Levels of MAOA and 5-HT 2 A Receptor in Patients With Pathological Internet Use: Correlations With Comorbid Symptoms.

Objective: Uncontrolled internet use may lead to the emergence of pathological internet use (PIU). PIU has become a global public health concern that can cause a range of psychotic symptoms, including anxiety, depression, and impulse control disorder. To date, we know very little about the principal biological factors related to PIU. Monoamine oxidase type A (MAOA) and serotonin (5-HT) 5-HT2A receptor (5-HT2AR) play critical roles in the development of behavioural and drug addictions. Thus, the aim of this study was to measure the relative expression of mRNA of MAOA and 5-HT2AR in peripheral blood mononuclear cells (PBMCs) of patients with PIU and to determine the correlations between these biological indicators and the comorbid symptoms of patients with PIU.Methods: In this study, the mRNA of MAOA and 5-HT2AR was detected using real-time PCR in PBMCs of the patients with PIU (n = 24) and healthy controls (HCs, n = 25). The relationship between the mRNA levels of MAOA and 5-HT2AR and clinical symptoms in patients with PIU was further investigated.Results: MAOA mRNA in PBMCs was significantly upregulated in patients with PIU compared with that in HCs. mRNA levels of 5-HT2AR were not found to differ significantly between HCs and patients with PIU. Correlation analyses further revealed a significant positive correlation between the relative expression of MAOA mRNA in PBMCs of patients with PIU and the Young's Internet Addiction Test and Self-Rating Depression Scale scores.Conclusion: The present study revealed upregulated expression of MAOA mRNA in patients with PIU and an association between the expression of MAOA mRNA and clinical symptoms of PIU, suggesting that the neurobiological changes may be similar between PIU and substance addiction. Additionally, this study demonstrated a potential association between comorbid symptoms and mRNA levels of MAOA.

The Positive Modulation Effect of a 6-Week Consumption of an Anthocyanin-Rich Mulberry Milk on Working Memory, Cholinergic, and Monoaminergic Functions in Healthy Working-Age Adults.

Due to the increase of stress-related memory impairment accompanying with the COVID-19 pandemic and financial crisis, the prevention of cognitive decline induced by stress has gained much attention. Based on the evidence that an anthocyanin-rich mulberry milk demonstrated the cognitive enhancing effect, we hypothesized that it should be able to enhance memory in working-age volunteers who are exposed to working stress. This study is an open-label, two-arm randomized study. Both men and women volunteers at age between 18 and 60 years old were randomly assigned to consume the tested product either 1 or 2 servings daily for 6 weeks. All subjects were assessed for cortisol, acetylcholinesterase (AChE), monoamine oxidase (MAO), monoamine oxidase type A (MAO-A), and monoamine oxidase type B (MAO-B) in saliva, and their working memory was determined both at baseline and at a 6-week period. The results showed that the working memory of subjects in both groups was enhanced at the end of the study period together with the reduction of saliva cortisol. The suppression of AChE, MAO, and MAO-A was also observed in subjects who consumed the tested product 2 servings daily. Therefore, we suggest the memory enhancing effect of an anthocyanin-rich mulberry milk. The possible mechanism may occur primarily via the suppression of cortisol. In addition, the high dose of mulberry milk also suppresses AChE, MAO, and MAO-A.

Monoamine oxidase A inhibition with moclobemide enhances the anti-parkinsonian effect of L-DOPA in the MPTP-lesioned marmoset.

Whereas monoamine oxidase (MAO) type B inhibitors are used as adjunct to L-3,4-dihydroxyphenylalanine (L-DOPA) in the treatment of Parkinson's disease (PD), the enzyme MAO type A (MAO-A) also participates in the metabolism of dopamine in the human and primate striatum. Here, we sought to assess the effect of the selective reversible MAO-A inhibitor moclobemide on L-DOPA anti-parkinsonian in the gold standard animal model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. We also assessed the effect of moclobemide on L-DOPA-induced dyskinesia and psychosis-like behaviours (PLBs). Experiments were performed in six MPTP-lesioned marmosets chronically treated with L-DOPA and exhibiting stable dyskinesia and PLBs upon each administration. In a randomised within-subject design, animals were administered a therapeutic dose of L-DOPA in combination with moclobemide (0.1, 1 and 10mg/kg) or its vehicle, after which the severity of parkinsonism, dyskinesia, and PLBs was rated by an experienced blinded rater. Moclobemide significantly reduced the global parkinsonian disability (- 36% with 0.1mg/kg, P < 0.05; - 38% with 1mg/kg, P < 0.01; - 47% with 10mg/kg, P < 0.01), when compared with its vehicle. This reduction of parkinsonism was not accompanied by an exacerbation of dyskinesia or PLBs. Reversible MAO-A inhibition with moclobemide appears as an effective way to increase the anti-parkinsonian action of L-DOPA, without negatively affecting dyskinesia or dopaminergic psychosis.

Ayahuasca - potential therapeutic properties in psychiatry. Research review.

Ayahuasca, also known as "the liana of the soul" and "the vine of the soul" is a ritual psychedelic traditionally administered in the form of plant decoction, used by the indigenous people of South America for centuries, and in the last 25 years also in Europe, Asia, Africa, Australia, Canada, and the United States. Its biological activity results from the content of N,N-dimethyltryptamine (DMT), acting mainly as a non-selective agonist of serotonin receptors and beta-carboline alkaloids, which are strong and short-acting monoamine oxidase type A(MAOI-A) inhibitors. For many years there have been reports of both the anti-anxiety and antidepressant effects of ayahuasca, as well as indications of the possibility of its use in the treatment of addictions. The results of studies of its effectiveness in drug-resistant depression seem to be promising, comparable in the opinion of some authors with the effect of therapeutic action of ketamine. In the article, we try to explain the complex profile of action and the resulting potential benefits, but also the risk of interaction and adverse effects associated with the taking of ayahuasca, which is important given the high variability of herbal mixtures used to produce the decoction.

Imitation of phase I metabolism reactions of MAO-A inhibitors by titanium dioxide photocatalysis

The imitation of phase I metabolism of moclobemide and toloxatone, two monoamine oxidase type A (MAO-A) inhibitors, was performed with the use of titanium dioxide photocatalytic process. Ultra high pressure liquid chromatography system coupled with an accurate hybrid ESI-Q-TOF mass spectrometer was used for the evaluation of metabolic profiles, structural elucidation of the identified transformation products and quantitative analysis of the process. Based on high resolution MS and MS/MS data, eleven transformation products were characterized in photocatalytic experiments for moclobemide and seven products for toloxatone. A significant number of these products were found as hepatic metabolites under the incubation of the selected MAO-A inhibitors with human liver microsomes (HLM). What is important, some of these HLM metabolites are not yet described in the literature. It was also found that the multivariate chemometric analysis allowed an effortless characterization of the registered metabolic profiles which can be a useful method for a fast preliminary drug metabolism study. Additionally, principal component analysis (PCA) of the registered TOF (MS) photocatalytic and HLM profiles of moclobemide and toloxatone shows that shorter irradiation time is preferred for photocatalytic metabolism experiments. A heterogeneous photocatalysis with the use of titanium dioxide was found to be a powerful tool for mimicking phase I metabolic reactions, as a fast, sensitive and inexpensive method.

Apium graveolens extract influences mood and cognition in healthy mice.

Apium graveolens is a food flavoring which possesses various health promoting effects. This study investigates the effect of a sub-acute administration of A. graveolens on cognition and anti-depression behaviors via antioxidant and related neurotransmitter systems in mice brains. Cognition and depression was assessed by various models of behavior. The antioxidant system of glutathione peroxidase (GPx), % inhibition of superoxide anion (O2-), and lipid peroxidation were studied. In addition, neurochemical parameters including acetylcholinesterase (AChE) and monoamine oxidase-type A (MAO-A) were also evaluated. Nine groups of male mice were fed for 30days with different substances-a control, vehicle, A. graveolens extract (65-500mg/kg), and reference drugs (donepezil and fluoxetine). The results indicated that the effect of the intake of A. graveolens extract (125-500mg/kg) was similar to the reference drugs, as it improved both spatial and non-spatial memories. Moreover, there was a decrease in immobility time in both the forced swimming and tail suspension tests. In addition, the A. graveolens extract reduced lipid peroxidation of the brain and increased GPx activity and the % inhibition of O2-, whereas the activities of AChE and MAO-A were decreased. Thus, our data have shown that the consumption of A. graveolens extract improved cognitive function and anti-depression activities as well as modulating the endogenous antioxidant and neurotransmitter systems in the brain, resulting in increased neuronal density. This result indicated an important role for A. graveolens extract in preventing age-associated decline in cognitive function associated with depression.

A Green and Convenient Route for the Regioselective Synthesis of New Substituted 3-Aryl-5H-indeno[1,2-c]pyridazines as Potential Monoamine Oxidase Type A Inhibitors

Several indeno[1,2-c]pyridazines were efficiently synthesised using the one-pot, three-component reaction of substituted indanones, arylglyoxalmonohydrates, and hydrazine in the presence of 1,5-diazabicyclo[4,3,0]non-5-ene (DBN) in water at room temperature. These substituted 3-aryl indeno[1,2-c]pyridazines can be considered as potential monoamine oxidase type A (MAOA) inhibitors. The advantages of this new strategy are the novelty of the indenopyridazine derivatives, high regioselectivity, use of water as the solvent, no requirement for toxic metal catalysts, and good to excellent yields.

The Relationship Between Academic Self-Efficacy and Academic-Related Boredom

The present study sought to examine the relationship between Chinese high school students’ academic self-efficacy and their academic-related boredom. Another objective was to explore the moderating effects of mono-amine-oxidase type A ( MAOA) gene polymorphism on this relationship. In a sample of 514 Chinese high school students, we measured their academic self-efficacy and academic-related boredom from Grades 10 to 12. In addition, we collected their DNA. Data were analyzed by using a linear mixture model. The results indicated that students’ academic self-efficacy negatively predicted their academic-related boredom. The relationship between academic self-efficacy and academic-related boredom was more reliable for students with the 3-repeat allele than for the students with the 4-repeat allele. The findings suggested that the functional polymorphism of MAOA gene moderated the relationship between academic self-efficacy and academic-related boredom.

Characterization of allele-specific expression of the X-linked gene MAO-A in trophectoderm cells of bovine embryos produced by somatic cell nuclear transfer.

Somatic cell nuclear transfer (SCNT) may affect epigenetic mechanisms and alter the expression of genes related to embryo development and X chromosome inactivation (XCI). We characterized allele-specific expression of the X-linked gene monoamine oxidase type A (MAO-A) in the trophectoderm (TF) of embryos produced by SCNT. Total RNA was isolated from individual biopsies (N = 25), and the allele-specific expression assessed by reverse transcription-polymerase chain reaction-restriction fragment length polymorphism. Both paternal and maternal alleles were expressed in the trophectoderm. However, a higher frequency of the mono-allelic expression of a specific allele was observed (N = 17; 68%), with the remaining samples showing the presence of mRNA from both alleles (N = 8; 32%). Considering that MAO-A is subject to XCI in bovine, our results suggest that SCNT may influence XCI because neither an imprinted (mono-allelic expression in all samples) nor a random (presence of mRNA from both alleles in all samples) pattern of XCI was observed in TF. Due to the importance of XCI in mammalian embryo development and its sensitivity to in vitro conditions, X-linked genes subject to XCI are candidates for use in the development of embryo quality molecular markers for assisted reproduction.

The upstream Variable Number Tandem Repeat polymorphism of the monoamine oxidase type A gene influences trigeminal pain‐related evoked responses

Monoamines have an important role in neural plasticity, a key factor in cortical pain processing that promotes changes in neuronal network connectivity. Monoamine oxidase type A (MAOA) is an enzyme that, due to its modulating role in monoaminergic activity, could play a role in cortical pain processing. The X-linked MAOA gene is characterized by an allelic variant of length, the MAOA upstream Variable Number Tandem Repeat (MAOA-uVNTR) region polymorphism. Two allelic variants of this gene are known, the high-activity MAOA (HAM) and low-activity MAOA (LAM). We investigated the role of MAOA-uVNTR in cortical pain processing in a group of healthy individuals measured by the trigeminal electric pain-related evoked potential (tPREP) elicited by repeated painful stimulation. A group of healthy volunteers was genotyped to detect MAOA-uVNTR polymorphism. Electrical tPREPs were recorded by stimulating the right supraorbital nerve with a concentric electrode. The N2 and P2 component amplitude and latency as well as the N2-P2 inter-peak amplitude were measured. The recording was divided into three blocks, each containing 10 consecutive stimuli and the N2-P2 amplitude was compared between blocks. Of the 67 volunteers, 37 were HAM and 30 were LAM. HAM subjects differed from LAM subjects in terms of amplitude of the grand-averaged and first-block N2-P2 responses (HAM>LAM). The N2-P2 amplitude decreased between the first and third block in HAM subjects but not LAM subjects. The MAOA-uVNTR polymorphism seemed to influence the brain response in a repeated tPREP paradigm and suggested a role of the MAOA as a modulator of neural plasticity related to cortical pain processing.

Rapid and sensitive fluorescent probes for monoamine oxidases B to A at low concentrations

A new monoamine oxidase (MAO) fluorescent probe that displays response for both monoamine oxidase type-A (MAO-A) and monoamine oxidase type-B (MAO-B) is reported. This sensing platform does not require any additional enzymes or reagents. Furthermore, the probes have better sensitivity and shorter response time by comparison with similar probes, and have potentials in differentiation of MAO-A and MAO-B upon further optimization.

The Monoamine Oxidase Type B Inhibitor Rasagiline in the Treatment of Parkinson Disease: Is Tyramine a Challenge?

Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "cheese effect," a hypertensive response to excess dietary tyramine, a biogenic sympathomimetic amine. Tyramine challenge studies, conducted to characterize rasagiline selectivity for the MAO-B enzyme and tyramine sensitivity, demonstrate that rasagiline, when used at the recommended dose, is selective for MAO-B and is not associated with heightened tyramine sensitivity. This conclusion is also supported by safety results from large clinical trials of rasagiline in Parkinson disease involving 2066 rasagiline-treated patients who did not require dietary tyramine restriction per protocol. In late 2009, US labeling for rasagiline was modified to state that dietary tyramine restrictions are not ordinarily required when rasagiline is administered at recommended doses. In addition, because rasagiline has been demonstrated to be selective for MAO-B at the approved dose of up to 1 mg/d, contraindications regarding concomitant use with sympathomimetic amines, use of sympathomimetic vasopressors in conjunction with general or local anesthesia, and use in patients with pheochromocytoma also were removed.

239 ALLELE-SPECIFIC EXPRESSION OF X CHROMOSOME-LINKED GENE MAO-A DURING PRE-IMPLANTATION DEVELOPMENT IN BOVINE EMBRYO

The in vitro embryo culture might affect epigenetic mechanisms, which are involved in controlling the expression of genes related to embryonic development and inactivation of X chromosome. Female mammals have 2 X chromosomes, and males have only 1. This has led to a particular mechanism of evolution of dosage compensation, called X-chromosome inactivation, an important epigenetic event that must occur in all mammalian female embryos. During embryogenesis, at the late blastocyst development (Xue F et al. 2002 Nature Genet. 31, 216–220), 1 of the 2 X chromosomes is randomly inactivated in each cell of the inner cell mass and preferentially X paternal in trophoblast. The aim of this study was to characterize the allele-specific expression of the X chromosome-linked gene monoamine oxidase type A (MAO-A) during in vitro pre-implantation embryo development in bovine. For phenotyping of the MAO-A gene, the RT-PCR restriction fragment length polymorphism technique was used. Primers were designed flanking a single nucleotide polymorphism and the sequence of forward inner primer creating a site of restriction to the RsaI enzyme, thus allowing the detection of allele-specific expression (Bos taurus Taurus × Bos taurus indicus). Oocytes were aspirated from 9 Nelore heifers homozygous for theA allele previously genotyped. The oocytes were selected, matured in vitro, and inseminated with X-sorted sperm from a Holstein bull homozygous for the G allele. Two pools of 10 heterozygous in vitro embryos of each developmental stage, 4-cell [44 h post-insemination (p.i.)], 8- to 16-cell (72 h p.i.), morula (144 h p.i.), blastocyst (156 p.i.), and expanded blastocyst (168 h p.i.), were produced and frozen until RNA extraction. Total RNA was extracted using Invisorb® Spin Cell RNA Mini Kit (Invitek, Berlin, Germany) according to the manufacturer’s protocol, and residual genomic DNA was removed with DNase I treatment. cDNA was done using Oligo dT primers (Invitrogen) and superscript III reverse transcriptase (Invitrogen). Nested PCR for each pool was performed and then the amplicons were digested with 10 U of RsaI enzyme (Promega, Madison, WI, USA). The products were separated by electrophoresis on a 3% agarose gel stained with ethidium bromide. The results showed that both alleles were expressionally represented in the 4-cell, 8- to 16-cell, and expanded blastocyst stages, with the X paternal allele disappearing in morula and blastocyst. We can conclude that both, maternal and paternal X chromosomes, are activated in the 2 earliest stages, inactivated in the morula and blastocyst stages, and reactivated in the expanded blastocyst stage. This research was supported by Embrapa Genetic Resources and Biotechnology and the Brazilian National Council for Scientific and Technological Development (CNPq).

How (Some) Criminals are Made

Some kids have bad luck. Kids who are abused, for example, tend to become abusers themselves. This is a brute sociological fact. Abused children are the unfortunate victims of poor antecedent and constitutive conditions that conduce to bad moral luck. In this paper, I hope to explain why this is the case, at least for some children, and (perhaps) especially for those who enter the world with low levels of monoamine oxidase type A (MAOA), a brain enzyme responsible for inhibiting neurotransmitters associated with aggression. I will also argue that individuals of this type (genetic predisposition (G)) coupled with abusive and/or neglectful early environments (E), have suffered from poor constitutive, antecedent, and circumstantial conditions that generate bad moral luck and, therefore, they are (a) less blameworthy than those who have not endured the combination of such conditions and (b) are, therefore, candidates for restorative justice: treatment and restorative justice for those who we know or prima facie should know suffer neurobiological deficits.

Serum Steroid Concentrations at Different Phases of Production and Brain Monoamine Oxidase Type A Messenger Ribonucleic Acid in Buller Steers

One field study was conducted to evaluate serum steroid hormone profiles of steers exhibiting characteristics attributed to buller steer syndrome and to assess the potential association between buller steer syndrome and the monoamine neurotransmitter enzyme monoamine oxidase type A (MAO-A) mRNA. Whole blood serum was collected at 3 time points from 600 crossbred steers: 1) before placement on intensively stocked early summer pastures (pregrass), 2) after arrival to a commercial feedlot (feedlot arrival; BW = 403 kg), and 3) when a steer exhibited classical buller characteristics (diagnosis of buller; n = 25). The pregrass progesterone period was suppressed (P < 0.05) only in sera obtained from bullers as compared with control animals (342 vs. 673 pg/mL). From feedlot arrival to the diagnosis of buller, a reduction (P < 0.05) in progesterone occurred in bullers (349 vs. 217 pg/mL). An increase (P < 0.05) in testosterone occurred in bullers from feedlot arrival to diagnosis of a buller (7.4 vs. 21.7 pg/mL). Estradiol-17β from bullers and controls increased (P < 0.01) from pregrass to feedlot arrival. Buller and control estradiol and testosterone levels were not different at any sampling time. From the same group of steers, 10 bullers and 12 controls, MAO-A mRNA levels were analyzed in postmortem samples removed from the frontal cortex region of the brain. The MAO-A mRNA levels measured by the real-time quantitative PCR method were 74.5% greater (P = 0.03) in bullers than controls. This study indicates bullers have suppressed serum concentrations of progesterone and a potential predisposition for heightened MAO-A activity.

Increase of monoamine oxidase-B activity in the brain of scrapie-infected hamsters

In the present study, the purpose is to determine activities of monoamine oxidases (MAO) in the brain of 263K scrapie-infected hamsters during the development of this experimental prion disease. Indeed, MAO activity modifications which have already been related in aging and neurodegenerations is suspected to be involved in the neuron loss process by elevated hydrogen peroxide formation. Monoamine oxidase type A (MAO-A) and B (MAO-B) activities were followed in the brain at different stages of the disease. MAO-A activity did not change significantly during the evolution of the disease. However, concerning the MAO-B activity, a significant increase was observed from 50 days post-infection and through the course of the disease and reached 42.9 ± 5.3% at its ultimate stage. Regarding these results, MAO-B could be a potential therapeutic target then we have performed a pre-clinical treatment with irreversible (Selegiline or l-deprenyl™) or and reversible (MS-9510) MAO-B inhibitors used alone or in association with an anti-scrapie drug such as MS-8209, an amphotericin B derivative. Our results show that none of the MAO-B inhibitors used was able to delay the onset of the disease. Neither these MAO-B inhibitors nor R-NMDA inhibitors (MK-801) can enhance the effects of MS-8209. The present findings clearly indicate a significant increase of cerebral MAO-B activity in scrapie-infected hamsters. Furthermore, inhibitors of MAO-B do not have any curative or palliative effect on this experimental model indicating that the raise of this activity is probably more a consequence rather than a causal event of the neurodegenerative process.