MAO-A Research Articles

Aggressiveness in Italian Children with ADHD: MAOA Gene Polymorphism Involvement.

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Small molecule probes for the specific imaging of monoamine oxidase A and monoamine oxidase B

AbstractMonoamine oxidases (MAOs) are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central nervous system. Furthermore, expression of MAOs is associated with the functions of peripheral organs. Dysfunction of MAOs is relevant in a variety of diseases such as neurodegenerative diseases, heart failure, metabolic disorders, and cancers. Monoamine oxidases have two isoenzymes, namely, monoamine oxidase A (MAO‐A) and monoamine oxidase B (MAO‐B). Therefore, the development of reliable and specific methods to detect these two isoenzymes is of great significance for the in‐depth understanding of their functions in biological systems, and for further promoting the clinical diagnosis and treatment of MAO‐related diseases. This review mainly focuses on the advances in small molecular probes for the specific imaging of MAO‐A and MAO‐B, including radiolabeled probes, fluorescent probes, and a 19F magnetic resonance imaging probe. In addition, applications of these probes for detecting MAO expression levels in cells, tissues, animal models, and patients are described. Finally, the challenges and perspectives of developing novel MAO imaging probes are also highlighted.

Abstract 2011: MAOA Drives Anti Androgen Therapy Resistance in Advanced Prostate Cancer by Conferring Neuroendocrine Plasticity via a Twist1 BRN2 Signaling Pathway

Abstract Background: Therapy resistance in cancer is often linked to cancer cell state or lineage changes. In prostate cancer (PCa), a subset of castration-resistant prostate cancer (CRPC) loses reliance on the androgen receptor (AR) signaling and gains neuroendocrine (NE) traits through a lineage switch along disease progression. However, the molecular mechanisms driving such cellular lineage plasticity remain unclear. This study investigated the functional and mechanistic role of monoamine oxidase A (MAOA) in driving adenocarcinoma (adeno)-to-NE lineage conversion in CRPC cells upon enzalutamide (ENZ), a FDA-approved newer-generation antiandrogen drug, and evaluated the efficacy of MAOA inhibitors for treating CRPC and overcoming ENZ resistance.Methods: ENZ-resistant C4-2B and CWR-R1 cells (C4-2BENZR and CWR-R1ENZR) CRPC cells were transfected with a PSA promoter-driven GFP expression construct for isolating a PSAlo/− cell population distinct from PSAhi cells, which was used for manipulation of MAOA expression levels and subsequent functional assays in vitro and in vivo. The MAOA expression levels were determined and correlated with NE parameters in PCa clinical samples by immunohistochemistry and data mining of multiple publicly available clinical datasets. Results: MAOA protein expression was significantly upregulated in the PSAlo/− ENZ-resistant cell population, accompanied by concomitant activation of NE markers and downregulation of luminal markers including AR and AR targets, compared to the PSAhi counterpart. Elevated MAOA expression was also found in PCa patient samples associated with NE features from multiple independent cohorts. Silencing MAOA suppressed the proliferation, migration, invasion, stem-like properties and NE plasticity of both PSAlo/- C4-2BENZR and CWR-R1ENZR cells. Moreover, co-culturing adeno LNCaP or C4-2B cells with MAOA-silenced PSAlo/- cells exhibiting a repressed secretory phenotype attenuated acquired induction of NE markers and proliferation of adeno cells as compared to controls. Mechanistically, MAOA induces Twist1, which directly activates the transcription and expression of BRN2, a master neural transcription factor known to confer NE differentiation and anti-AR therapy resistance in CRPC. Further, pharmacological inhibition of MAOA greatly enhanced the growth-inhibitory efficacy of ENZ with ENZ sensitivity restored in ENZ-resistant LuCaP PC PDX-derived organoids as well as a PSAlo/− CWR-R1ENZR xenograft mouse model.Conclusion: Our results suggest MAOA as a potential therapeutic target for reversing ENZ resistance in CRPC treatment by blockade of NE transdifferentiation.Funding Acknowledgements: This work was supported by the NIH/NCI grants R37CA233658 and R01CA258634 (to B. Wu) and the DOD Department of Defense EIRA award W81XWH-21-1-0218 (to J. Wei) Citation Format: Jing Wei, Jing Wang, Chia-hui Chen, Wen Guan, Boyang Wu. MAOA Drives Anti Androgen Therapy Resistance in Advanced Prostate Cancer by Conferring Neuroendocrine Plasticity via a Twist1 BRN2 Signaling Pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2011.

Deficits in emotion recognition and processing in children with high callous-unemotional traits: the role of the MAOA gene.

Children with high Callous-Unemotional (CU) traits show deficits in recognizing and processing facial expressions. Alterations in emotion recognition have been linked to a higher synaptic concentration of monoaminergic neurotransmitters. The current study investigated the relationship between the MAOA-Low-activity alleles and the ability to recognize and process facial expressions in 97 male children (8-12years old) diagnosed with disruptive behavior disorder. Participants completed a computerized emotion-recognition task while an eye-tracking system recorded the number (Fixation Count, FC) and length (Fixation Duration, FD) of fixations to the eye region of the emotional stimuli. Children with high CU traits exhibited lower scores in recognition of sadness and anger, and lower FC and FD for sadness and fear than children with low CU traits. Children carrying the MAOA-Low-activity alleles displayed lower FD for sadness, and FD and FC for fear than those carrying the MAOA-High-activity alleles. These genetic effects appeared even stronger in children with CU traits. Moderation analysis revealed that CU traits were associated with lower FC and FD for fear, and lower FD for sadness, probably due to the MAOA-Low-activity alleles. Our findings, although to be replicated, suggest MAOA-Low-activity alleles as potential genetic biomarkers to identify CU children in need of training focused on emotion processing.

Melatonin attenuates fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice

Melatonin is a neurohormone synthesized by the pineal gland to regulate the circadian rhythms and has proven to be effective in treating drug addiction and dependence. However, the effects of melatonin to modulate the drug-seeking behavior of fentanyl and its underlying molecular mechanism is elusive. This study was designed to investigate the effects of melatonin on fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice. The accompanying changes in the expression of Brain and Muscle Arnt-Like (BMAL1), tyrosine hydroxylase (TH), and monoamine oxidase A (MAO-A) in relevant brain regions including the suprachiasmatic nucleus (SCN), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus (Hip) were investigated by western blot assays to dissect the mechanism by which melatonin modulates fentanyl - induced behavioral sensitization and circadian rhythm disorders. The present study suggest that fentanyl (0.05, 0.1 and 0.2 mg/kg) could induce behavioral sensitization and melatonin (30.0 mg/kg) could attenuate the behavioral sensitization and circadian rhythm disorders in mice. Fentanyl treatment reduced the expression of BMAL1 and MAO-A and increased that of TH in relevant brain regions. Furthermore, melatonin treatment could reverse the expression levels of BMAL1, MAO-A, and TH. In conclusion, our study demonstrate for the first time that melatonin has therapeutic potential for fentanyl addiction.

An in vitro analysis of an innovative standardized phospholipid carrier-based Melissa officinalis L. extract as a potential neuromodulator for emotional distress and related conditions.

Background: Melissa officinalis L. (MO), commonly known as lemon balm, a member of the mint family, is considered a calming herb. In various traditional medicines, it has been utilized to reduce stress and anxiety and promote sleep. A growing body of clinical evidence suggests that MO leaf extract supplementation possesses considerable neuropharmacological properties. However, its possible mechanism of action largely remains unknown. Objective: In the present in vitro studies, we comparatively investigated the central nervous system (CNS)-calming and antioxidative stress properties of an innovative standardized phospholipid carrier-based (Phytosome™) MO extract (Relissa™) vs. an unformulated dry MO extract. Methods: The neuropharmacological effect of the extract was studied in the anti-depressant enzymes γ-aminobutyrate transaminase (GABA-T) and monoamine oxidase A (MAO-A) assays and SH-SY5Y cells brain-derived neurotrophic factor (BDNF) expression assay. The neuroprotective effect of the extract against oxidative stress was assessed in SH-SY5Y cell-based (H2O2-exposed) Total Antioxidant Status (TAS) and Total Reactive Oxygen Species (ROS) assays. The cytotoxic effect of the extract was evaluated using MTT and LDH assays. The extract antioxidant effect was also evaluated in cell-free chemical tests, including TEAC-ABTS, DPPH, Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Antioxidant Capacity (ORAC), and Hydroxyl Radical Antioxidant Capacity (HORAC) assays. Results: Relissa™ exhibited high GABA-T inhibitory activity, IC50 (mg/mL) = 0.064 vs. unformulated dry MO extract, IC50 (mg/mL) = 0.27. Similar inhibitory effects were also observed for MAO-A. Relissa™ demonstrated an improved neuroprotective antioxidant effect on SH-SY5Y cells against H2O2-induced oxidative stress. Compared to unformulated dry MO extract, Relissa™ exerted high protective effect on H2O2-exposed SH-SY5Y cells, leading to higher cells BDNF expression levels. Moreover, cell-free chemical tests, including TEAC-ABTS, DPPH radical scavenging, FRAP, ORAC, and HORAC assays, validated the improved antioxidant effect of Relissa™ vs. unformulated dry MO extract. Conclusion: The results of the present study support the neuromodulating and neuroprotective properties of Relissa™, and its supplementation may help in the amelioration of emotional distress and related conditions.

Design, synthesis, in silico, and in vitro evaluation of novel benzyloxybenzene substituted (S)-α-amino amide derivatives as cholinesterases and monoaminoxidases inhibitor.

In this study, a series of novel benzyloxybenzene substituted (S)-α-amino acid methyl esters and their amide derivatives were synthesized and evaluated for their inhibitory actions against acetylcholinesterase(AChE), butyrylcholinesterase(BChE), monoamine oxidase A(MAO-A), and monoamine oxidase B(MAO-B). The synthetic strategy was based on starting from benzyl bromide (5) and 4-hydroxybenzaldehyde (6). The reaction of 5 and 6 in the presence of K2 CO3 gave benzyloxybenzaldehyde 7. Benzyloxybenzene substituted (S)-α-amino acid methyl esters 11, 12, 13, (±)-19, and (±)-20 were obtained from the reaction of L-amino acid methyl esters with benzyloxybenzaldehyde (7) followed by in situ reduction with NaBH4 . The reaction of (S)-11, (S)-12, 13, (±)-19, and (±)-20 with excess ammonia gave amides (S)-14, (S)-15, 16, (±)-21, and (±)-22. The in vitro inhibitory activities of compounds against MAO-A,MAO-B, AChE, and BChEwere investigated. Within the α-amino acid methyl ester series, 13 (21.32 ± 0.338 µM) showed selectivity by inhibiting the MAO-B better than MAO-A. 13 emerged as the most active member of this series, exhibiting a 12-fold selectivity for MAO-B. 14 (4.501 ± 0.295 µM) demonstrated a pronounced selectivity for MAO-A over MAO-B, with a selectivity ratio of 110-fold. In addition, it was determined that compound 15 (95.65 ± 3.09 µM) had high selectivity for BChE inhibition. 21was demonstrated the most potent inhibition (18.36 ± 1.36 µM) against AChE.

Differential responses to UCP1 ablation in classical brown versus beige fat, despite a parallel increase in sympathetic innervation

In the cold, the absence of the mitochondrial uncoupling protein 1 (UCP1) results in hyper-recruitment of beige fat, but classical brown fat becomes atrophied. Here we examine possible mechanisms underlying this phenomenon. We confirm that in brown fat from UCP1-knockout (UCP1-KO) mice acclimated to the cold, the levels of mitochondrial respiratory chain proteins were diminished; however, in beige fat, the mitochondria seemed to be unaffected. The macrophages that accumulated massively not only in brown fat but also in beige fat of the UCP1-KO mice acclimated to cold did not express tyrosine hydroxylase, the norepinephrine transporter (NET) and monoamine oxidase-A (MAO-A). Consequently, they could not influence the tissues through the synthesis or degradation of norepinephrine. Unexpectedly, in the cold, both brown and beige adipocytes from UCP1-KO mice acquired an ability to express MAO-A. Adipose tissue norepinephrine was exclusively of sympathetic origin, and sympathetic innervation significantly increased in both tissues of UCP1-KO mice. Importantly, the magnitude of sympathetic innervation and the expression levels of genes induced by adrenergic stimulation were much higher in brown fat. Therefore, we conclude that no qualitative differences in innervation or macrophage character could explain the contrasting reactions of brown versus beige adipose tissues to UCP1-ablation. Instead, these contrasting responses may be explained by quantitative differences in sympathetic innervation: the beige adipose depot from the UCP1-KO mice responded to cold acclimation in a canonical manner and displayed enhanced recruitment, while the atrophy of brown fat lacking UCP1 may be seen as a consequence of supraphysiological adrenergic stimulation in this tissue.

MICROMERIA MYRTIFOLIA BOISS. & HOHEN’İN BİYOLOJİK AKTİVİTELERİNİN BELİRLENMESİ

Objective: Lamiaceae family has a wide variety of well-known and lesser-known plants with strong medicinal qualities. The genus Micromeria Benth. is a member of this family consisting of herbaceous plants with a variety of significant biological, phytochemical, and ethnobotanical uses. In this study, the biological activities of methanol and ethanol extracts of Micromeria myrtifolia were evaluated. Material and Method: To demonstrate the antioxidant activity DPPH radical scavenging activity and total phenolic content assays were done. The effects of the extracts on acetylcholinesterase (AChE) and monoamine oxidase-A were then assessed. Result and Discussion: Methanol extract showed the highest DPPH scavenging activity, at the dose of 10 mg/ml with a value of 96.55%. For the highest concentration that can be applicable, AChE inhibitions for the methanol and ethanol extracts were 25% and 27%, respectively. On the other hand, the inhibitory effects of the ethanol and methanol extracts of the plant on MAO-A were determined; for the ethanol extract IC50 value was found as 32.5876 ± 0.89 g/ml, and for the methanol extract it was found as 34.6544 ± 0.76 g/ml. It can be told that M. myrtifolia can act as a potential antioxidant. With further research and investigation, it is thought that Micromeria myrtifolia could be used as a natural source for the treatment of various neurological diseases.

Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage.

Monoamine oxidase and xanthine oxidase inhibitors represent useful multi-target drugs for the prevention, attenuation, and treatment of oxidative damage and neurodegenerative disorders. Chimeric molecules, constituted by naturally derived compounds linked to drugs, represent lead compounds to be explored for the discovery of new synthetic drugs acting as enzyme inhibitors. We have previously reported that seven hydroxytyrosol-donepezil hybrid compounds play a protective role in an in vitro neuronal cell model of Alzheimer's disease. In this work, we analyzed the effects exerted by the hybrid compounds on the activity of monoamine oxidase A (MAO-A) and B (MAO-B), as well as on xanthine oxidase (XO), enzymes involved in both neurodegenerative disorders and oxidative stress. The results pointed to the identification, among the compounds tested, of selective inhibitors between the two classes of enzymes. While the 4-hydroxy-3-methoxyphenethyl 1-benzylpiperidine-4-carboxylate- (HT3) and the 4-hydroxyphenethyl 1-benzylpiperidine-4-carboxylate- donepezil derivatives (HT4) represented the best inhibitors of MAO-A, with a scarce effect on MAO-B, they were almost ineffective on XO. On the other hand, the 4,5-dihydroxy-2-nitrophenethyl 1-benzylpiperidine-4-carboxylate donepezil derivative (HT2), the least efficient MAO inhibitor, acted like the best XO inhibitor. Therefore, the differential enzymatic targets identified among the hybrid compounds synthesized enhance the possible applications of these polyphenol-donepezil hybrids in neurodegenerative disorders and oxidative stress.

A GAPDH serotonylation system couples CD8+ T cell glycolytic metabolism to antitumor immunity

Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8+ Tcells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8+ Tcells and contributes to antitumor immunity. CD8+ Tcells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8+ Tcells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification.

Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.

A mechanistic link between depression and risk of arrhythmias could be attributed to altered catecholamine metabolism in the heart. Monoamine oxidase-A (MAO-A), a key enzyme involved in catecholamine metabolism and longstanding antidepressant target, is highly expressed in the myocardium. The present study aimed to elucidate the functional significance and underlying mechanisms of cardiac MAO-A in arrhythmogenesis. Analysis of the TriNetX database revealed that depressed patients treated with MAO inhibitors had a lower risk of arrhythmias compared with those treated with selective serotonin reuptake inhibitors. This effect was phenocopied in mice with cardiomyocyte-specific MAO-A deficiency (cMAO-Adef), which showed a significant reduction in both incidence and duration of catecholamine stress-induced ventricular tachycardia compared with wild-type mice. Additionally, cMAO-Adef cardiomyocytes exhibited altered Ca2+ handling under catecholamine stimulation, with increased diastolic Ca2+ reuptake, reduced diastolic Ca2+ leak, and diminished systolic Ca2+ release. Mechanistically, cMAO-Adef hearts had reduced catecholamine levels under sympathetic stress, along with reduced levels of reactive oxygen species and protein carbonylation, leading to decreased oxidation of Type II PKA and CaMKII. These changes potentiated phospholamban (PLB) phosphorylation, thereby enhancing diastolic Ca2+ reuptake, while reducing ryanodine receptor 2 (RyR2) phosphorylation to decrease diastolic Ca2+ leak. Consequently, cMAO-Adef hearts exhibited lower diastolic Ca2+ levels and fewer arrhythmogenic Ca2+ waves during sympathetic overstimulation. Cardiac MAO-A inhibition exerts an anti-arrhythmic effect by enhancing diastolic Ca2+ handling under catecholamine stress.

Near-Infrared Fluorescence Probe for Monoamine Oxidase A with a Large Stokes Shift for Intraoperative Navigation.

Monoamine oxidase A (MAO-A) is a dimeric flavoprotein that is found in the mitochondrial membrane. Currently, there is a lack of near-infrared fluorescent probes (NIR-FPs) with good specificity and high sensitivity for detecting MAO-A, making it difficult to accurately recognize and image cells in vitro and in vivo. In this study, the NIR-FP DDM-NH2 was designed and synthesized in order to detect MAO-A specifically in live biological systems. The probe comprised two functional components: dicyanoisophosphone as an NIR dye precursor and alanine as a recognition moiety. After identifying MAO-A, the probe exhibited an NIR emission peak at 770 nm with a significant Stokes shift (180 nm), 11-fold response factor, low detection limit of 99.7 nM, and considerably higher affinity toward MAO-A than that toward MAO-B, indicating high sensitivity. In addition, DDM-NH2 was effective when applied to the image-based assessment of MAO-A activity in HeLa cells, zebrafish, and tumor-bearing mice, demonstrating great potential for visualization-based research and MAO-A application in vivo.

Association of MAOA Gene Polymorphisms with aggressive behaviors of some prisoners in Erbil city / Kurdistan region, Iraq

Association of MAOA Gene Polymorphisms with aggressive behaviors of some prisoners in Erbil city / Kurdistan region, Iraq

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

BackgroundSerotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database.ResultsNone of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites.ConclusionsMethylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression

Depression has been linked to the dysfunction of the autonomic nervous system, which may cause dysregulation of the cardiovascular system. One promising therapeutic strategy for treating different diseases is inhibiting the enzyme fatty acid amide hydrolase (FAAH), which increases the availability of endogenous cannabinoids. We examined the effect of chronic FAAH inhibition with URB597 treatment on the noradrenaline (NA) content, synthesis, transport, and degradation in the left ventricle of female and male rats exposed to chronic unpredictable stress (CUS). CUS decreased the levels of both NA and dopamine-?-hydroxylase (DBH) protein in male rats and decreased NA transporter (NET) protein levels in female rats while elevating monoamine oxidase A (MAO-A) in both sexes. Intraperitoneal URB597 application led to increased expression of DBH in stressed males, as well as elevated NET protein levels and decreased MAO-A protein levels in the left ventricle of stressed rats of both sexes. URB597 treatment may have a beneficial effect on the cardiovascular system in an animal model of depression with heightened sympathoneural activity.

Usability of MAO-A gene in the judicial process

Monoamine oxidase (MAO-A) is an enzyme found in the nervous system and plays an important role in the breakdown of monoamine neurotransmitters. This enzyme varies among individuals depending on genetic factors. The monoamine oxidase-A (MAO-A) gene has been studied by various researchers to understand behavioral differences between individuals and evaluate crime propensity. However, serious ethical and legal problems may arise regarding the use of genetic factors alone in the judicial process. In this context, considering environmental factors as well as the MAO-A gene may contribute to the development of a more comprehensive approach. The role of the MAO-A gene in the judgment process has created an area of research that allows us to understand behavioral differences. The MAO-A gene has been associated with various behavioral traits. It has particular effects on aggressive behavior, antisocial behavior, and emotional reactions. In this context, the MAO-A gene may be an important factor in determining how individuals respond to environmental factors and guide their judgment processes. Some studies show that individuals with low MAO-A activity may be prone to antisocial behavior and crime. Thus, the MAO-A gene can be taken into consideration in determining guilt in legal processes. Assessing individuals' criminal propensity based on genetic factors can make the justice system more effective and fair. For example, harsh childhood conditions or traumatic experiences can trigger genetic predispositions and increase criminal propensity. In this case, it is important to take environmental factors into account when evaluating the genetic profile of the individual during the judicial process. Many ethical and legal issues need to be carefully considered on how to integrate the MAO-A gene into the judicial system. Therefore, research on the usability of the MAO-A gene in the judicial process should be continued.

Monoamine oxidase A probe synthesis and fluorescence imaging in cells and zebrafish based on AIE mechanism

Monoamine oxidase A (MAO-A) is a crucial mammalian flavoenzyme that plays a significant role in various neurodegenerative diseases such as depression, Parkinson’s disease, schizophrenia, and epilepsy, as well as cancer, cardiac disorders, and liver disease. Thus, a real-time and targeted MAO-A detection approach is desperately needed to study the onset and management of disorders linked to MAO-A. In this study, we have successfully synthesized a red-emitting fluorescent probe AIE-M, which is based on the specificity of MAOs for the structural catalysis of propylamine group substrates. This probe utilizes quinoline-malononitrile (QM) with AIE properties as the fluorescent master. The probe containing QM exhibits excellent aggregation-induced luminescence (AIE), biocompatibility, and high photostability, enabling specific recognition of MAO-A. Moreover, it can be employed for the detection and imaging of endogenous MAO-A in neuroblastoma cells and zebrafish, thereby offering a novel research instrument for diagnosing associated ailments.

Monoamine Oxidase-A (MAO-A) Inhibitors Screened from the Autodisplayed Fv-Antibody Library.

Serotonin-like mimotopes were screened from the Fv-antibody library to be used as inhibitors against monoamine oxidase A (MAO-A). The Fv-antibody [corresponding to the VH region of immunoglobulin G (IgG)] consists of three complementarity-determining regions and four frame regions. The Fv-antibody library was prepared by site-directed mutagenesis of CDR3, which consists of 11 amino acid residues. Three target clones were screened from the Fv-antibody library, and the binding affinity of the screened clones to the monoclonal anti-serotonin antibody was analyzed using fluorescence-activated cell sorting. The screened Fv-antibodies were expressed as soluble proteins fused with green fluorescence protein. Additionally, the screened CDR3 regions (11 residues) of the selected Fv-antibodies were synthesized as peptides with linking amino acid residues. The binding constants (KD) of the three serotonin-like mimotopes (Fv-antibodies and peptides) were estimated using a surface plasmon resonance biosensor. The inhibitory activity (IC50) of the serotonin-like mimotopes (Fv-antibodies and peptides) was estimated separately for MAO-A and MAO-B enzymes and compared with that of conventional inhibitors. Finally, the screened serotonin-like mimotopes were used to treat a cell line (SH-SY5Y, ATCC code: CRL-2266) expressing serotonin receptors. This was done to confirm the following two aspects: (1) the binding of mimotopes to the serotonin receptors on the cell surface and (2) the inhibitory activity of mimotopes against MAO-A enzymes in the cell lysates.

The Mechanism of Anxiolytic Effects of Moringa oleifera Leaf Extracts Associated with Significant Differential Expression of Crhb, Faah2a, Mao, and Pah Genes in Danio rerio

The search and development of new therapeutic agents from medicinal plants to alleviate anxiety is well justified due to the increasing cases of anxiety disorder and lack of effective treatment. Moringa oleifera has been used traditionally to treat anxiety. However, there is still lack of understanding on the mechanism for its anxiolytic effect. The purpose of this study was to investigate the anxiolytic effects and the mechanism of ethanolic extracts of the leaves of M. oleifera (MOLE) by observing behavioural changes of the Danio rerio and the differential gene expression analysis using custom RT2 Profiler PCR array. A 14-day chronic behaviour study was conducted using three concentrations of MOLE (500 mg/L, 1000 mg/L and 2000 mg/L) fluoxetine as the positive control. Stress-induced D. rerio treated with 1000 mg/L MOLE showed the lowest level of anxiety compared to other groups as evidenced by a decrease in freezing episodes and freezing time, increased entries into the light region. The fish also showed significant changes in the expression of crhb, faah2a, mao, and pah genes. MOLE with the presence of quercetin and kaempferol are believed to exert its anxiolytic effects through differential expression of gene (i) modulating the function of GABAA receptor (crhb), (ii) inhibiting the expression of nitric oxide synthase (NOS) and the production of nitric oxide, (iii) increasing the AEA levels in the brain (faah2a), (iv) increasing the level of dopamine levels in the brain (mao). These findings provide valuable insights into the potential use of MOLE as a treatment for anxiety-related disorders as well as the significance of the molecular pathways involved in its anxiolytic properties.