Immuno-fluorescence cytochemistry on thin frozen sections of human substantia nigra for staining of monoamine oxidase A and monoamine oxidase B: a pilot study

Moll, Georg; Moll, Ralf; Riederer, Peter; Gsell, W.; Heinsen, Helmut; Denney, Richard M.

doi:10.1007/978-3-7091-9113-2_8

Cited by 6 publications

(6 citation statements)

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“…Identified adrenergic cell groups ClLC3 expressed high levels of MAO-A mRNA, in agreement with the reported protein localization (e.g., Arai et al, 1986;Saura et al, 1992). The existence of MAO-A in the dopaminergic system has been the subject of much debate (Westlund et al, 1985(Westlund et al, , 1988Arai et al, 1986;Konradi et al, 1988Konradi et al, , 1989Willoughby et al, 1988;Moll et al, 1990). Our finding of a low but significant level of MAO-A (but not of MAO-B) mRNA expression in identified dopaminergx neurons of the substantia nigra compacta, therefore, indicates a putative role for MAO-A in the in vivo deamination of DA.…”

Section: Catecholaminergic Cell Groupssupporting

confidence: 70%

“…. However, evidence for the expected levels of MAO-A in serotoninergic and dopaminergic neurons is lacking (Westlund et al, 1985(Westlund et al, , 1988Konradi et al, 1988;Willoughby et al, 1988;Moll et al, 1990;Richards et al, 1992;Saura et al, 1992Saura et al, , 1995. Both isoenzymes are likely to exist in glial cells, although there is less convincing evidence for MAO-A (Konradi et al, 1988(Konradi et al, , 1989Westlund et al, 1988Westlund et al, ,1993 than for MAO-B (Maeda et al, 1987;Konradi et al, 1988Konradi et al, , 1989Westlund et al, 1988;Nakamura et al, 1990;Ekblom et al, 1993;Kitahama et al, 1994;Saura et al, 1994).…”

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confidence: 99%

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Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system

Luque

Kwan

Abell

et al. 1995

J of Comparative Neurology

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Monoamine oxidases A and B (MAO-A and MAO-B) oxidatively deaminate neurotransmitter and xenobiotic amines. The cellular localization of these isoenzymes in the central nervous system (CNS) differs markedly and only partly reflects the distribution of their presumed natural substrates. In the present study, by using in situ hybridization with 35S-labelled oligonucleotide probes, we examined the distribution of mRNAs encoding MAO-A and MAO-B in the rat CNS. Probes for tyrosine hydroxylase, histidine decarboxylase, and tryptophan hydroxylase mRNAs were used to demonstrate the catecholaminergic, histaminergic, or serotoninergic nature of some cell populations in adjacent sections. The radioligands [3H]-Ro 41-1049 and [3H]lazabemide (reversible and selective inhibitors of MAO-A and MAO-B, respectively) were used to reveal the protein distribution by enzyme radioautography. The distribution and abundance of transcripts for both isoenzymes in the tissues investigated differed markedly but, in general, correlated with the protein distribution. MAO-A mRNA and protein were most abundant in noradrenergic neurons. However, moderate levels of transcript expression and protein were also detected in the serotoninergic neurons, and low but significant levels were detected in the dopaminergic neurons. An unexpectedly remarkable degree of hybridization signal was apparent in nonaminergic cell populations, e.g., in the cerebral cortices, the hippocampal formation (CA1-3, dentate gyrus), the cerebellar granule cell layer, and the spinal cord motoneurons. In contrast, MAO-B mRNA and protein were most abundant in serotoninergic and histaminergic neurons, Bergmann glial cells, and circumventricular organs, including the ependyma. MAO-B transcripts were also weakly expressed in nonaminergic cells, e.g., in the hippocampal formation (CA1-2). A further nonneuronal localization of MAO-B transcripts was also resolved, e.g., in the glia limitans, the olfactory nerve layer, and the cerebellar peduncle. These findings reveal further the potential of various cell populations to synthesize the isoenzymes, and homologous (aminergic) and heterologous (nonaminergic) patterns of expression as well as coexpression of MAO mRNAs are described.

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Section: Catecholaminergic Cell Groupssupporting

confidence: 70%

mentioning

confidence: 99%

Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system

Luque

Kwan

Abell

et al. 1995

J of Comparative Neurology

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“…MAO-A is detectable in cells that release these monoamines, with the highest levels in norepinephrine releasing neurons (Konradi et al 1988(Konradi et al , 1989Luque et al 1995;Moll et al 1990;Saura et al 1996); however, MAO-A is also present in cells that do not release monoamines, such as astrocytes and glia (Youdim et al 2006). Within cells, MAO-A is mainly located on outer mitochondria membranes.…”

Section: Monoamine Oxidase a Monoamines And Moodmentioning

confidence: 97%

Neurochemical Imaging and Depressive Behaviours

Meyer

2012

Current Topics in Behavioral Neurosciences

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Neurochemical imaging is frequently applied to measure markers of pathological change so as to understand mechanisms that create symptoms of major depressive disorder. For example, indices of greater monoamine oxidase A(MAO-A) level, particularly in the prefrontal and anterior cingulate cortex, are associated with depressed mood states, and high-risk states for onset of major depressive episodes. MAO-A metabolises monoamines, and greater metabolism of monoamines occurs when MAO-A is elevated in brain. Lower extracellular serotonin is associated with greater pessimism in humans and chronic serotonin deficiency is associated with upregulation of 5-HT2A (serotonin2A) receptors in cortex. During major depressive episodes when pessimism is more severe, greater 5-HT2A BPND, an index of density occurs in prefrontal and anterior cingulate cortex. These results argue for a mechanism of lowering extracellular serotonin in the prefrontal and anterior cingulate cortex, consequent to elevated MAO-A level. The relationship between elevated 5-HTT BPND and greater pessimism during major depressive episodes suggests that greater 5-HTT density in the context of elevated MAO-A level further contributes to serotonin deficiency in these brain regions. A similar mechanism may explain the association between neuroimaging indices of greater dorsal striatal D2 density, DAT density and symptoms of motor retardation: Greater MAO-A level and relatively greater DAT density lower extracellular dopamine in the dorsal striatum, leading to motor retardation. Indices of greater 5-HT1A density, particularly in the cingulate cortex, have been associated with major depressive disorder, and well as anxiety disorders, suggesting that this abnormality is mechanistically related to presence of anxiety symptoms. To date, abnormalities of Glx a measure reflecting glutamate and glutamine levels have been most strongly associated with presence of major depressive episodes, with greater levels in occipital cortex, and reduced levels in prefrontal cortex. Ultimately, the future for neurochemical imaging is to better understand the mechanisms that predispose toward onset of MDE so as to create biologically informed, novel, methods of prevention, and superior, more symptom-targeted treatments.

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“…However, although the melanin-containing A9 cells appeared to contain more MAO-A than MAO-B, a hybridization signal for neither MAO-A nor MAO-B mRNA could be detected . Enzyme histochemical and immunohistochemical investigations have failed to demonstrate the presence of either enzyme in the majority of A9 cells (Konradi et al, 1988;Westlund et al, 1988;Moll et al, 1990). The functional implications of these findings are currently the subject of much speculation.…”

Section: Distribution and Abundance Of Mao-a And Mao-b In Human Brainmentioning

confidence: 99%

Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19- 6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain

et al. 1992

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Monoamine oxidases A and B (MAO-A and MAO-B) oxidatively deaminate neurotransmitter and xenobiotic amines. Since the cellular localization of the isoenzymes in the CNS and peripheral organs determines to a large extent which substrate has access to which isoenzyme, knowledge of their tissue distribution and cellular localization is essential. Here we describe how reversible and selective inhibitors of MAO-A and MAO-B [Ro 41–1049 and Ro 19–6327 (lazabemide), respectively] can be used, as tritiated radioligands, to map the distribution and abundance of the enzymes in microscopic regions of the rat CNS and peripheral organs, and human brain by quantitative enzyme radioautography. The in vitro binding characteristics of both radiolabeled inhibitors revealed them to be selective, high-affinity ligands for the respective enzymes. KD and Bmax values for 3H-Ro 41–1049 in rat cerebral cortex were 10.7 nM and 7.38 pmol/mg protein, respectively, and for 3H-Ro 19–6327 were 18.4 nM and 3.45 pmol/mg protein, respectively. In accordance with their potencies as enzyme inhibitors, binding to MAO-A and MAO-B was competitively inhibited by clorgyline (IC50 = 1.4 nM) and L-deprenyl (selegiline; IC50 = 8.0 nM), respectively. The capacities of various rat and human tissues to bind the radioligands correlated extremely well with their corresponding enzyme activities. As revealed by the respective binding assays, the distribution and abundance of MAO-A and MAO-B in the tissues investigated differed markedly. MAO-A was most abundant in the locus coeruleus, paraventricular thalamus, bed nucleus of the stria terminalis, median habenular nucleus, ventromedial hypothalamus, raphe nuclei, solitary tract nucleus, inferior olives, interpeduncular nucleus, claustrum, and numerous peripheral tissues, including liver, vas deferens, heart, superior cervical ganglion, and exocrine and endocrine pancreas. In contrast, MAO-B was most abundant in the ependyma, circumventricular organs, olfactory nerve layer, periventricular hypothalamus, cingulum, hippocampal formation, raphe nuclei, paraventricular thalamus, mammillary nuclei, cerebellar Bergmann glia cells, liver, posterior pituitary, renal tubules, and endocrine pancreas. The cellular localization of the isoenzymes in both rat and human brain differs markedly and does not reflect the distribution of the presumed natural substrates, for example, absence of MAO-A in serotoninergic neurons. Indeed, the present evidence suggests that, whereas MAO-A is found in noradrenergic and adrenergic neurons, MAO-B occurs in astrocytes, serotoninergic neurons, as well as ventricular cells, including most circumventricular organs. The physiological roles of the enzymes are discussed in the light of these findings, some of which were unexpected.(ABSTRACT TRUNCATED AT 400 WORDS)

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Immuno-fluorescence cytochemistry on thin frozen sections of human substantia nigra for staining of monoamine oxidase A and monoamine oxidase B: a pilot study

Cited by 6 publications

References 2 publications

Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system

Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system

Neurochemical Imaging and Depressive Behaviours

Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19- 6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain

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