Quantitative distribution of rat brain monoamine oxidase A by [14C]clorgyline autoradiography

Abstract

The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [14C]clorgyline in normal, conscious rat brain. [14C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [14C]methyliodide. Sixty minutes after [14C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.

Potential Metabolic Bioactivation Pathways Involving Cyclic Tertiary Amines and Azaarenes

“…Extensive metabolic, biochemical, and toxicological investigations (2,3,(50)(51)(52) have established that the neurodegenerative properties of MPTP are mediated by the MAO-B-generated pyridinium metabolite MPP + (25). The selective toxicity of MPTP is remarkable since the target nigrostriatal neurons do not catalyze the bioactivation reaction (53) presumably because they lack MAO-B activity (54)(55)(56). This dilemma appears to have been resolved by the demonstration that MPP + is concentrated in the dopaminergic nigrostriatal nerve terminals via the dopamine transporter (57,58).…”

Specific binding of [18F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain

“…We see a focus of notably high MAO‐A binding in the habenula, which is previously reported to contain 1.6 nmol/g MAO‐A based on quantitative autoradiography with [ 14 C]clorgyline (Kondoh et al . ); only the locus coeruleus and interpeduncular nucleus had higher MAO‐A binding in that study; we have earlier discerned [ 11 C]harmine binding in the locus coeruleus of living pigs (Jensen et al . ), but this was not evident in the present [ 18 F]FEH study, presumably because of greater effects of partial volume with μPET.…”

“…We found the MAO-A densities in rat brain to range from 337 pmol/g in cerebellum (the region of lowest abundance) to 836 pmol/g in the thalamus (the region of highest abundance). We see a focus of notably high MAO-A binding in the habenula, which is previously reported to contain 1.6 nmol/g MAO-A based on quantitative autoradiography with [ 14 C]clorgyline (Kondoh et al 1994); only the locus coeruleus and interpeduncular nucleus had higher MAO-A binding in that study; we have earlier discerned [ 11 C]harmine binding in the locus coeruleus of living pigs (Jensen et al 2006), but this was not evident in the present [ 18 F]FEH study, presumably because of greater effects of partial volume with lPET. The rank order and magnitude of present autoradiographic findings in vitro in cerebellum, striatum, and cerebral cortex match closely the results obtained earlier with [ 14 C]clorgyline, the irreversible ligand.…”

Non‐MAO A binding of clorgyline in white matter in human brain

“…2001a), preventing the examination of white matter binding in this species. However, autoradiographic studies in the rat brain with a saturating dose of [ 14 C]clorgyline (1 mg/kg) report almost uniform distribution of C‐14 (except for locus coeruleus) in different brain regions after clorgyline pre‐treatment (10 mg/kg) to inhibit MAO A binding (Kondoh et al . 1994).…”

“…Irreversible binding of labeled clorgyline in vivo has been demonstrated in mouse and rat brain (MacGregor et al . 1985; Kondoh et al . 1994).…”