Noradrenaline storage function of species-specific protein bodies, markers of monoamine neurons in human locus coeruleus demonstrated by dopamine-β-hydroxylase immunogold localization

Abstract

Our histochemical and ultrastructural studies have identified, in human catecholamine locus coeruleus (LC) neurons, abundant and large spherical protein bodies (PB), containing histone-like, arginine-rich proteins, which originate as dense bodies in mitochondria. This species-specific phenotype in the neurons of man is highly intriguing. In the electron microscope PB are disrupted in LC neurons in depressed individuals, where noradrenaline is known to be reduced. This coincidence of ultrastructure and neurochemistry raises the question whether these bodies could qualify as noradrenaline-storing organelles in the human LC. Our rationale was to examine, in known model tissues that contain catecholamines—sympathetic ganglia and tumors of the autonomic nervous system—if vesicles show the same fine structure and histochemistry as the PB of the human LC. Hence, we selected biopsy tissues of five ganglioneuromas and postmortem tissues of LC from 25 control subjects. Since dopamine-β-hydroxylase (DBH) is a hallmark of noradrenaline identity and present in dense core vesicles, the investigation of DBH localization with the immunogold method constituted the experiment of choice for this study. Histochemical determinations of arginine with Carmoisine L, and of lipids with Rhodamine B complemented the study of similarities between the PB of the human LC and ganglioneuromas. Our results showed, with the colloidal gold method, that DBH immunogold labeling was localized in the core and in the double membranes of the PB, and also in the adjacent mitochondria. These results indicate that protein bodies (a) are unequivocal storage vesicles of noradrenaline, and (b) derive from regular mitochondria and represent a new phenotype in man, which is probably an evolutionary adaptation of amine-storing organelles.