Monoamine oxidases — activities, genotypes and the shaping of behaviour

Oreland, Lars; Nilsson, Kent W.; Damberg, Mattias; Hallman, Jarmila

doi:10.1007/s00702-007-0694-8

Cited by 60 publications

(48 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This has been further substantiated by experiments showing a weaker serotonergic innervation in the brains of MAOA knockout mice (Gaspar et al 2003). Thus, it is tempting to speculate that MAOA-VNTR mainly plays a functional role during fetal development (Fowler et al 2007;Oreland et al 2007) and that the association between MAOA genotype and MAOA enzyme activity diminishes with age. Possible factors contributing to a decrease in the association between MAOA enzyme activity and MAOA genotype in the adult brain might be hormones (Sanchez et al 2005;Smith et al 2004) and/or epigenetic mechanisms (Pinsonneault et al 2006).…”

Section: Discussionmentioning

confidence: 90%

Maltreatment, MAOA, and Delinquency: Sex Differences in Gene–Environment Interaction in a Large Population-Based Cohort of Adolescents

et al. 2010

Self Cite

View full text Add to dashboard Cite

The present study investigated a possible interaction between a functional polymorphism in the MAOA gene promoter (MAOA-VNTR) and childhood maltreatment in the prediction of adolescent male and female delinquency. A cohort of 1,825 high school students, 17-18 years old, completed an anonymous questionnaire during class hours which included questions on childhood maltreatment, sexual abuse, and delinquency. Saliva samples were collected for DNA isolation, and analyzed for the MAOA-VNTR polymorphism. Self-reported maltreatment was a strong risk factor for adolescent delinquent behavior. The MAOA genotype also showed a significant main effect when controlled for maltreatment. Boys with a short variant and girls with one or two long variants of the polymorphism showed a higher risk for delinquency when exposed to maltreatment. Our results confirm previous findings of an interaction between the MAOA-VNTR polymorphism and self-reported maltreatment. Results for boys and girls differ according to MAOA-VNTR genotype and direction of phenotypic expression.

show abstract

Section: Discussionmentioning

confidence: 90%

Maltreatment, MAOA, and Delinquency: Sex Differences in Gene–Environment Interaction in a Large Population-Based Cohort of Adolescents

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, total congenital deficiency of MAO-A results in Brunner syndrome, a rare X-linked recessive disorder chacterized by aggressive conduct and criminal acts (such as armed violence, rape, and arson) in the affected males (Brunner et al, 1993). Allelic variants of MAO-A polymorphisms associated to low enzymatic activity are not inherently conducive to aggressive or violent behavior (Alia-Klein et al, 2008; Caspi et al, 2002;Kim-Cohen et al, 2006), but are nevertheless associated with alterations in the processing of emotional and social inputs (Lee and Ham, 2008;Williams et al, 2009), and a significantly higher risk for antisocial personality disorder in male carriers Caspi et al, 2002;Meyer-Lindenberg et al, 2006;Oreland et al, 2007).…”

Section: Introductionmentioning

confidence: 98%

Social Deficits and Perseverative Behaviors, but not Overt Aggression, in MAO-A Hypomorphic Mice

Bortolato¹,

Chen²,

Godar³

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

Monoamine oxidase (MAO)-A is a key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE). In humans and mice, total MAO-A deficiency results in high 5-HT and NE levels, as well as elevated reactive aggression. Here we report the generation of MAO-A(Neo) mice, a novel line of hypomorphic MAO-A mutants featuring the insertion of a floxed neomycin-resistance cassette in intron-12 of the Maoa gene. This construct resulted in a chimeric, non-functional variant of the Maoa-Neo transcript, with a truncated C-terminus, likely due to aberrant splicing; these deficits notwithstanding, small amounts of functional Maoa transcript were found in the brain of MAO-A(Neo) mice. In the prefrontal cortex and amygdala, MAO-A(Neo) mice showed low, yet detectable, MAO-A catalytic activity, as well as 5-HT levels equivalent to WT littermates; conversely, the hippocampus and midbrain of MAO-A(Neo) mice featured a neurochemical profile akin to MAO-A-knockout (KO) mice, with undetectable MAO-A activity and high 5-HT concentrations. MAO-A(Neo) mice showed significant increases in dendritic length in the pyramidal neurons of orbitofrontal cortex, but not basolateral amygdala, in comparison with WT littermates; by contrast, the orbitofrontal cortex of MAO-A KO mice showed significant reductions in basilar dendritic length, as well as a profound increase in apical dendritic length. MAO-A(Neo) mice showed a unique set of behavioral abnormalities, encompassing reduced open-field locomotion, perseverative responses, such as marble burying and water mist-induced grooming, and a lack of anxiety-like behaviors in the elevated plus-maze and light-dark box paradigms. Notably, whereas MAO-A(Neo) and KO mice showed significant reductions in social interaction, only the latter genotype showed increases in resident-intruder aggression. Taken together, our findings indicate that MAO A hypomorphism results in behavioral and morphological alterations distinct from those featured by MAO-A KO mice.

show abstract

“…Its inhibitors, used as antidepressant drugs for over 50 years, have been shown to raise brain amine levels. The observation that inhibition of MAO increases monoaminergic function has supported a long-running drug discovery effort to find novel drugs that inhibit MAO to treat mood and degenerative disorders, including depression, aggression, schizophrenia, hyperactivity, Parkinson's Disease (PD), and Alzheimer's Disease (AD) (Oreland, 2004, Murphy et al, 2006, Oreland et al, 2007, Fisar et al, 2010, Bortolato and Shih, 2011, Song et al, 2013.…”

Section: Introductionmentioning

confidence: 99%

Molecular aspects of monoamine oxidase B

Ramsay

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

Graphical abstract Highlights• MAO B activity depends on both amine and oxygen concentrations KeywordsMonoamine oxidase B; kinetics; drug design; neurotransmitter levels; platelet AbbreviationsAlzheimer's Disease, AD; Parkinson's Disease, PD; dopamine transporter, DAT; serotonin transporter, SERT; noradrenaline transporter, NET; the vesicular transporter, VMAT; Gprotein coupled receptor, GPCR; induced pluripotent stem cells, iPSC; serotonin reuptake inhibitor, SSRI; brain-derived neurotrophic factor, BDNF; multi-target designed ligands, MTDL; IC 50 , the concentration of compound required to inhibit a specified assay by 50%; K i , a kinetically measured inhibitor dissociation constant. Word count -approx 5490 (excluding references). Abstract 196 words.3

show abstract

Monoamine oxidases — activities, genotypes and the shaping of behaviour

Cited by 60 publications

References 57 publications

Maltreatment, MAOA, and Delinquency: Sex Differences in Gene–Environment Interaction in a Large Population-Based Cohort of Adolescents

Maltreatment, MAOA, and Delinquency: Sex Differences in Gene–Environment Interaction in a Large Population-Based Cohort of Adolescents

Social Deficits and Perseverative Behaviors, but not Overt Aggression, in MAO-A Hypomorphic Mice

Molecular aspects of monoamine oxidase B

Contact Info

Product

Resources

About