Monoamine oxidase

Monoamine oxidases (MAO) (

In humans there are two types of MAO: MAO-A and MAO-B.^[7]

• Both are found in
  astroglia
  .
• Outside the central nervous system:
  • MAO-A is also found in the
    gastrointestinal tract, and placenta
    .
  • MAO-B is mostly found in blood platelets.

MAO-A appears at roughly 80% of adulthood levels at birth, increasing very slightly after the first 4 years of life, while MAO-B is almost non-detectable in the infant brain. Regional distribution of the monoamine oxidases is characterized by extremely high levels of both MAOs in the hypothalamus and hippocampal uncus, as well as a large amount of MAO-B with very little MAO-A in the striatum and globus pallidus. The cortex has relatively high levels of only MAO-A, with the exception of areas of the cingulate cortex, which contains a balance of both. Autopsied brains demonstrated the predicted increased concentration of MAO-A in regions dense in serotonergic neurotransmission, however MAO-B only correlated with norepinephrine.^[8]

Other studies, in which the activities of MAO (not protein amounts) were examined in rat brain, revealed the highest MAO-B activity in the median eminence of hypothalamus. Dorsal raphe nucleus and medial preoptic area have relatively high MAO-B activity, but much lower than MAO-B activity in the median eminence.^[9][10] Among cerebral endocrine glands, pineal gland has high MAO-B activity (its median value is lower than that for median eminence and higher than that for medial preoptic area).^[10] Pituitary has the lowest level of MAO-B activity when compared with brain areas studied.^[9]

Function

Monoamine oxidases catalyze the

• epinephrine are mainly broken down by MAO-A.^{[medical citation needed}
  ]
• Phenethylamine and benzylamine are mainly broken down by MAO-B.^{[medical citation needed]}
• Both forms metabolize dopamine, tyramine, and tryptamine;^[14] however, some evidence suggests MAO-B may not be responsible for a significant amount of dopamine degradation.^[15]

Specific reactions catalyzed by MAO include:

• noradrenaline to 3,4-Dihydroxymandelic acid;^{[medical citation needed}
  ]
• Metanephrine or normetanephrine to vanillylmandelic acid (VMA);^{[medical citation needed]}
• dihydroxyphenylacetic acid;^{[medical citation needed}
  ]
• 3-Methoxytyramine to homovanillic acid.^{[medical citation needed]}

Clinical significance

Because of the vital role that MAOs play in the inactivation of

In fact, MAO-A inhibitors act as antidepressant and anti-anxiety agents, whereas MAO-B inhibitors are used alone or in combination to treat Alzheimer's disease and Parkinson's disease.^[23] Some research suggests that certain phenotypes of depression, such as those with anxiety, and "atypical" symptoms involving psychomotor retardation, weight gain and interpersonal sensitivity respond better to MAO inhibitors than other classes of anti-depressant. However the findings related to this have not been consistent.^[24] MAOIs may be effective in treatment resistant depression, especially when it does not respond to tricyclic antidepressants.^[25]

Parasite interactions

Sleeping sickness - caused by trypanosomes - gets its name from the sleep disruption it causes in mammals. That sleep disruption is caused, at least in part, by trypanosomes' tendency to disrupt MAO activity in the orexin system.^[26]

Animal models

There are significant differences in MAO activity in different species. Dopamine is primarily deaminated by MAO-A in rats, but by MAO-B in vervet monkeys and humans.^[27]

Mice unable to produce either MAO-A or MAO-B display autistic-like traits.^[28] These knockout mice display an increased response to stress.^[29]

Arthropods

Insects

Insect brains express MAOs,^[30][31][32] and some insecticides^[33][32] work by inhibiting them. An MAOI effect is especially important for chlordimeform^[33][32][34] (although one result shows little or no effect in Periplaneta americana);^[35] and dieldrin may^[30] or may not^[31] be an MAOI in Locusta migratoria.^{[medical citation needed]}

Acari

MAO activity has been detected in Rhipicephalus microplus and chlordimeform is an MAOI in R. m..^[36]

Genetics

The genes encoding MAO-A and MAO-B are located side-by-side on the short arm of the X chromosome, and have about 70% sequence similarity. Rare mutations in the gene are associated with Brunner syndrome.^{[medical citation needed]}

A study based on the

The claim that an interaction between low MAO-A activity and maltreatment would cause anti-social behavior has been criticized since the predisposition towards anti-social behavior could equally well have been caused by other genes inherited from abusive parents.[38]

A possible link between predisposition to

Unlike many other enzymes, MAO-B activity is increased during aging in the brain of humans and other mammals.[41] Increased MAO-B activity was also found in the pineal gland of aging rats.^[10] This may contribute to lowered levels of monoamines in aged brain and pineal gland.^[10][42]

See also

• Cheese effect
• I₂ receptor
• Monoamine oxidase inhibitor

References