Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system.
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.
Luque
J M
JM
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basle, Switzerland.
Kwan
S W
SW
Abell
C W
CW
Da Prada
M
M
Richards
J G
JG
D000818:Animals; D001345:Autoradiography; D015415:Biomarkers; D002490:Central Nervous System / Q000166:cytology* / Q000201:enzymology*; D006632:Histamine / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism; D015345:Oligonucleotide Probes; D010848:Picolinic Acids / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013462:Sulfur Radioisotopes; D013844:Thiazoles / Q000378:metabolism
D015415:Biomarkers; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D015345:Oligonucleotide Probes; D010848:Picolinic Acids; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D013844:Thiazoles; C063456:Ro 41-1049; C059303:lazabemide; D006632:Histamine; D008995:Monoamine Oxidase