Distinct monoamine oxidase A and B populations in primate brain

Monoclonal antibodies specific for monoamine oxidase (MAO) A and MAO B, respectively, were used to localize these enzymes in primate brain. The reagents recognized different populations of neurons: those that recognized MAO A were located in cell groups containing catecholamines, including the substantia nigra, nucleus locus coeruleus, nucleus subcoeruleus, and the periventricular region of the hypothalamus, whereas those that recognized MAO B were observed in serotonin regions, including the nucleus raphe dorsalis and nucleus centralis superior. These data illustrate the physiological independence of MAO A and B and show that neurons may be specialized for their degradative as well as their synthetic functions.     

Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET

The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L-deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L-[11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures.     

Alterations in the pattern of amine excretion in man produced by a monoamine oxidase inhibitor

The administration of monoamine oxidase inhibitors produces an increase in the urinary excretion of many amines for which efficient alternate routes of metabolism are not available. These include tryptamine, paratyramine, and a "metatyramine-like" substance. The inhibitors can therefore be used to detect previously unsuspected pathways of amino acid decarboxylation. The finding that the excretions of norepinephrine, epinephrine, 3,4-dihydroxyphenylethylamine, and possible serotonin are not appreciably affected are consistent with previous reports of the existence of alternative metabolic routes.     

On the reported inhibition of monoamine oxidase by an agent with sedative properties

1-Benzyl-2-methyl-5-methoxytryptamine has been reported, on the basis of indirect evidence, to inhibit monoamine oxidase. More direct experiments, however, demonstrate that the drug is devoid of the ability to block monoamine oxidase in brain in vitro or in vivo.     

Histochemical demonstration in rat of monoamine oxidase inhibition of beta-phenyl-isopropyl hydrazine

A histochemical method for demonstration of monoamine oxidase activity was found to be almost as sensitive as a biochemical method when used for revealing total inhibition of monoamine oxidase in rat tissues after administration of beta-phenyl-isopropyl hydrazine. The histochemical method is of special value in the study of monoamine oxidase inhibition in the complex structures of the brain.     

Somatosensory thalamic neurons: effects of cortical depression

Deafferented somatosensory thalamic neurons showed hyperactivity, followed by greatly reduced activity, after initiation of cortical spreading depression; local cooling of sensorimotor cortex was followed only by the inactive phase. Stimulation of contralateral midbrain reticular formation during the inactive phase failed to induce the typical increase in discharge rate of somatosensory thalamic neurons, but produced desynchronization in unaffected cortex. These results indicate that corticothalamic discharge is necessary for sustaining the ongoing activity of deafferented somatosensory thalamic neurons and for maintaining their responsiveness to stimulation of the reticular formation.     

Metabolism of adrenaline after blockade of monoamine oxidase and catechol-O-methyltransferase

Experiments in cats infused with 5 micromole of dl-adrenaline-2-C(14) showed that blockade of either monoamine oxidase or catechol-O-methyltransferase is largely compensated for by the activity of the intact enzyme system; combined blockade of both enzyme systems results in the formation of a new adrenaline catabolite and in the increased production of acidic, mainly conjugated, catabolites, the identity of which remains to be established.     

Brain monoamine oxidase in mice after exposure to aggression and defeat

Effects on the monoamine Oxidase activity of the hypothalamus, amygdala, and frontal cortex of untrained mice exposed to repeated defeat by trained fighters for two 5-minute periods a day for 0, 1, 2, 4, 8, 14, or 20 days were studied. Activity in the hypothalamus increased significantly during the first 2 days of fighting, while the activity in the amygdala and frontal cortex remained essentially unchanged. After 8 days, activity in all three brain areas declined. After 14 days of fighting the monoamine Oxidase activity returned to normal, but another decrease was observed in the three areas after 20 days of fighting.     

Reduced monoamine oxidase activity in platelets: a possible genetic marker for vulnerability to schizophrenia

Monoamine oxidase activity in blood platelets was measured, with [(14)C]tryptamine as substrate, in 13 monozygotic twin pairs discordant for schizophrenia and in 23 normal volunteers. The monoamine oxidase activity of both schizophrenic and nonschizophrenic co-twins was significantly lower than it was for the normals, and it was highly correlated between twins. In addition, there was a significant inverse correlation between a measure of the degree of the schizophrenic disorder and the monoamine oxidase activity. These data suggest, but do not prove, that reduced platelet monoamine oxidase activity may provide a genetic marker for vulnerability to schizophrenia.     

A correlation between platelet monoamine oxidase activity and plasma prolactin concentrations in man

Increases in plasma prolactin concentrations produced by alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, varied inversely with baseline platelet monoamine oxidase activity in 12 patients with chronic schizophrenia. In normal volunteers with low monoamine oxidase activity and in unmedicated patients with chronic schizophrenia, plasma prolactin concentrations varied directly with platelet monoamine oxidase activity. No such relationship was found in normal subjects with high platelet monoamine oxidase activity. These data suggest that platelet monoamine oxidase activity reflects monoaminergic activity in the tubero-infundibular system, which in turn affects plasma prolactin concentrations. This relationship may be important in patients with low platelet monoamine oxidase activity, such as some chronic schizophrenics.     

A low threshold calcium spike mediates firing pattern alterations in pontine reticular neurons

Intracellular electrical recordings in an in vitro slice preparation of the brainstem medial pontine reticular formation, a region thought to be important in mediation of desynchronized sleep phenomena, demonstrate a population of neurons that have a calcium-dependent, low threshold spike. This low threshold spike was inactivated at relatively depolarized membrane potential levels and, when this spike was deinactivated, it induced a burst of action potentials. The membrane potential dependence of the spike may underlie changes in action potential firing patterns associated with behavioral state change because the baseline membrane potential in neurons of the medial pontine reticular population depolarizes during passage from waking and slow wave sleep to desynchronized sleep, which is characterized by the absence of burst firing.     

Atriopeptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas

Antisera to atriopeptin III and to a cyanogen bromide fragment of the precursor molecule atriopeptigen were prepared and used to examine the distribution of atriopeptin-like immunoreactive material in the heart and brain of the rat. Granules of this material were seen in myocytes throughout the right and left atria and were densest in the perinuclear region. The distribution of atriopeptin-like immunoreactive material in the heart is consistent with previous reports of atrial secretory granules. In the brain neurons containing the material were observed in the hypothalamus and the pontine tegmentum. Atriopeptin in the brain may serve as a neurotransmitter in neural systems controlling blood volume and composition, the same physiological functions regulated by blood-borne atriopeptin.     

Muscarinic depression of long-term potentiation in CA3 hippocampal neurons

Behavioral studies have suggested that muscarinic cholinergic systems have an important role in learning and memory. A muscarinic cholinergic agonist is now shown to affect synaptic plasticity in the CA3 region of the hippocampal slice. Long-term potentiation (LTP) of the mossy fiber-CA3 synapse was blocked by muscarine. Low concentrations of muscarine (1 micromolar) had little effect on low-frequency (0.2 hertz) synaptic stimulation but did significantly reduce the magnitude and probability of induction of LTP. Experiments under voltage clamp showed that muscarine blocked the increase in excitatory synaptic conductance normally associated with LTP at this synapse. These results suggest a possible role for cholinergic systems in synaptic plasticity.     

Temperature-sensitive neurons in the brain of brook trout

The brain temperature of trout (Salvelinus fontinalis) was altered by perfusion of the gills with warm or cool water. Neuronal activity was recorded with microelectrodes. Twelve neurons responded to an increase in temperature with increased activity, and five neurons responded to a decrease in temperature with an increase in activity.     

Erythrocyte and brain forms of spectrin in cerebellum: distinct membrane-cytoskeletal domains in neurons

Chicken cerebellum expresses a polypeptide antigenically and biochemically related to the alpha subunit of spectrin, an erythrocyte membrane-cytoskeletal protein. Most of this polypeptide is associated with a brain specific spectrin subunit, gamma-spectrin, and is localized in virtually all neuronal cell bodies and processes. Cerebellum also expresses polypeptides antigenically related to the beta subunits of erythrocyte spectrin and these are also found in association with cerebellar alpha-spectrin but are confined to the plasmalemma of the neuronal cell bodies. This suggests that there is a mechanism for segregating different spectrin complexes into distinct membrane domains within a single cell.