Monoamine oxidase

Summary

Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases. MAOs are important in the breakdown of monoamines ingested in food, and also serve to inactivate monoamine neurotransmitters. Because of the latter, they are involved in a number of psychiatric and neurological diseases, some of which can be treated with monoamine oxidase inhibitors (MAOIs) which block the action of MAOs. Subtypes and tissue distribution In humans there are two types of MAO: MAO-A and MAO-B.

Both are found in neurons and astroglia.
Outside the central nervous system: ** MAO-A is also found in the liver, pulmonary vascular endothelium, g

Official source

https://en.wikipedia.org/wiki/Monoamine_oxidase

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Social deficits induced by peripubertal stress in rats are reversed by resveratrol

Guillaume Poirier, Maria del Carmen Sandi Perez, Olivia Zanoletti

Adolescence is increasingly recognized as a critical period for the development of the social system, through the maturation of social competences and of their underlying neural circuitries. The present study sought to test the utility of resveratrol, a dietary phenol recently reported to have mood lifting properties, in modulating social interaction that is deficient following early life adversity. The main aims were to 1) pharmacologically restore normative social investigation levels dampened by peripubertal stress in rats and 2) identify neural pathways engaged by this pharmacological approach. Following peripubertal (P28–42) stress consisting of unpredictable exposures to fearful experiences, at adulthood the subjects' propensity for social exploration was examined in the three-chamber apparatus, comparing time invested in social or non-social investigation. Administered intraperitoneally 30 min before testing, resveratrol (20 mg/kg) normalized the peripubertal stress-induced social investigation deficit seen in the vehicle group, selectively altering juvenile but not object exploration. Examination of prefrontal cortex subregion protein samples following acute resveratrol treatment in a separate cohort revealed that while monoamine oxidase A (MAOA) enzymatic activity remained unaltered, nuclear AKT activation was selectively increased in the infralimbic cortex, but not in the prelimbic or anterior cingulate cortex. In contrast, androgen receptor nuclear localization was increased in the prelimbic cortex, but not in the infralimbic or anterior cingulate cortex. This demonstration that social contact deficits are reversed by resveratrol administration emphasizes a prosocial role for this dietary phenol, and evokes the possibility of developing new treatments for social dysfunctions.

2014

Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments

Corrado Cali, Andrea Chicca, Nicole Déglon, Graham Knott, Luca Pucci, Tamara Zehnder

Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders.

2020

Stress can have a strong and long lasting effect on the establishment and maintenance of dominance hierarchies in rats. When two rats of a pair have not been stressed (non-stressed pair) before a first social encounter, they establish a dominance hierarchy, but the rank that is obtained during this first encounter is not maintained until a second encounter one week later. When one rat of the pair is stressed (stressed pair) before the first encounter, the stressed rat becomes subordinate during the first encounter and the hierarchy that is formed is long lasting and stable. In this thesis, the neurobiological mechanisms underlying the effects of stress on dominance hierarchies were studied. In the first study, we investigated the role of increasing corticosterone levels before or just after a first encounter between two rats of a pair in the establishment and the long-term maintenance of a dominance hierarchy. We show that pre-social encounter corticosterone treatment does not affect the outcome of the hierarchy during a first encounter, but induces a long-term memory for the hierarchy when the corticosterone-injected rat becomes dominant during the encounter, but not when it becomes subordinate. Post-social encounter corticosterone leads to a long-term maintenance of the hierarchy only when the subordinate rat of the pair is injected with corticosterone. This corticosterone effect implicates glucocorticoids in the consolidation of the memory for a recently established hierarchy. Next, we investigated the immediate and long-term changes in mRNA levels of receptors for oxytocin and vasopressin in medial amygdala and lateral septum. In subordinate rats of the stressed pairs, we found a downregulation in oxytocin receptor mRNA in medial amygdala at three hours after the first encounter, and a downregulation in vasopressin 1a receptor mRNA in lateral septum one week after the first encounter. We show that administration of an oxytocin antagonist in the medial amygdala of the subordinate rat immediately after a first encounter induces a long-term memory for the established hierarchy. Administration of a vasopressin 1a receptor antagonist in the lateral septum of the subordinate rat just before a second encounter mimics the effects of exposure to acute stress on the long-term establishment of a dominance hierarchy. These results suggest a role for oxytocin and vasopressin in the effects of stress on the long-term establishment of dominance hierarchies. Finally, we investigated the long-term effects of acute stress and hierarchy formation on the establishment of a second hierarchy with an unfamiliar opponent. We show that the behavior of stressed subordinate rats towards an unfamiliar opponent depends on the previous status of the opponent: when paired with a previously dominant rat they become subordinate, whereas they become dominant when paired with a previously subordinate rat. Furthermore, we show that monoamine oxidase A and androgen receptor mRNA levels are downregulated in the lateral septum of stressed subordinate rats at one week after the first encounter; i.e., at the time when we have observed their flexible social behavior against unfamiliar opponents. The monoamine oxidase A inhibitor clorgyline was injected into the lateral septum to examine whether there was a causal relationship between changes in monoamine oxidase A mRNA levels and offensive behavior towards an unfamiliar subordinate opponent. However, our results did not support this hypothesis. Taken together, we have shown that exposure to acute stress and a social encounter leads to changes in the mRNA levels of receptors for oxytocin, vasopressin and androgens and of monoamine oxidase A. These changes might underlie the effect of stress on the formation of a stable and long-lasting dominance hierarchy. Corticosterone plays a role in the long-term maintenance of the recently established hierarchy and hence it is an ideal candidate to mediate some of the observed neurobiological changes.

EPFL2011