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Amine-storing Organelles in Soma and Dendrites of Human Locus Coeruleus Neurons

Ismini Kloukina1*, Sophia Havaki2 and Margarita Chrysanthou-Piterou3
  • 1 Th. Th. Cozzika Foundation, Neurobiology Research Institute, Greece
  • 2 School of Medicine, University of Athens, Department of Histology and Embryology, Greece
  • 3 University of Athens, 1st Department of Psychiatry, Eginition Hospital, Greece

Previous studies have identified in human catecholamine neurons abundant spherical acidophilic protein bodies (PB), which originate from mitochondria retaining the double membrane (Issidorides et al., 1996). In locus coeruleus (LC), PB have somatodendritic distribution and are unequivocal storage vesicles for noradrenaline, as demonstrated by immunolocalization of Dopamine-β-Hydroxylase (Issidorides et al., 2004). This species-specific phenotype in man is the result of important physiological functions, because depletion or missing of PB is accompanied with Parkinson’s disease. The aim of this study was to investigate the composition of PB and their role in normal and pathological conditions.
Post mortem brain specimens of LC were collected from 13 control subjects and 12 cases of Parkinson’s disease patients. Human adrenal medulla was used as a model tissue and histochemical and immunohistochemical correlation between PB and chromaffin granules was made. At the ultrastructural level, colloidal gold method was used for the accurate localization of macromolecules, at high resolution. The mitochondrial origin of PB was sealed with their positive immunoreactivity for mitochondrial porin. The next purpose was to reinforce the identity of PB as monoamine storage sites and to assess their potential of somatodendritic release. For this reason we studied the subcellular immunolocalization of Chromogranin A (CgA) and Vesicular Monoamine Transporter 2 (VMAT2), given the fact that their localization defines the vesicles capacity of filling with monoamine and hence exocytotic release (Schafer et al., 2010; Li et al., 2005). The data provided, demonstrate the novel ultrastructural immunolocalization of both CgA and VMAT2 in PB, supporting their involvement in somatodendritic storage and release of noradrenaline in human LC.
In Parkinson’s disease, immunolocalization of VMAT2 in the LC revealed the reduction of protein compared to normal controls. Reduced expression of VMAT2 leads to defective sequestration of monoamines into vesicles, their accumulation in the cytoplasm and eventually the emergence of Parkinson’s disease phenotype. Parkinson’s disease is characterized by a progressive cellular deposition of the synaptic protein a-synuclein in diverse brain regions (Schulz, 2007). Along with the impairment of mitochondrial respiration, both mitochondrial fission/fusion have been shown to be altered (Cardoso, 2011). In view of the above, we investigated the mitochondrial ultrastructure in LC from Parkinson’s disease patients along with a-synuclein immunolocalization. The morphological study revealed disrupted mitochondrial ultrastructure indicating dysfunction in normal neurotransmitter-storing organelle production, leading to defective sequestration of monoamine into vesicles.
Immunolocalization of a-synuclein in Parkinson’s disease brains revealed the accumulation of this protein in different stages in physiologically appearing neurons, as well as, in mature brainstem Lewy bodies. At the electron microscope the subcellular localization of this protein in PB, as well as, in neuromelanin of LC neurons was revealed.
The study of PB, which are responsible for the somatodentritic storage and possible release of noradrenaline in human LC neurons, and their contribution in the formation of Lewy bodies, as indicated by the localization of common components among these two structures may be helpful towards the understanding of Parkinson’s disease.

References

Cardoso SM, 2011. The mitochondrial cascade hypothesis for Parkinson's disease. Curr Pharm Des. 17: 3390-7.

Issidorides MR, Havaki S, Arvanitis DL, Chrysanthou-Piterou M, 2004. Noradrenaline storage function of species-specific protein bodies, markers of monoamine neurons in human locus coeruleus demonstrated by dopamine-beta-hydroxylase immunogold localization. Prog Neuropsychopharmacol Biol Psychiatry. 28: 829-47.

Issidorides MR, Kriho V, Pappas GD., 1996. The fine structure of large dense-core organelles in human locus coeruleus neurons. Neurol Res. 18: 57-63.

Li H, Waites CL, Staal RG, Dobryy Y, Park J, Sulzer DL, Edwards RH, 2005. Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway confers the somatodendritic exocytosis of monoamines. Neuron. 48: 619-33.

Schafer MK, Mahata SK, Stroth N, Eiden LE, Weihe E, 2010. Cellular distribution of chromogranin A in excitatory, inhibitory, aminergic and peptidergic neurons of the rodent central nervous system. Regul Pept. 165: 36-44.

Schulz JB, 2007. Mechanisms of neurodegeneration in idiopathic Parkinson's disease. Parkinsonism Relat Disord. 13: S306-8.

Keywords: Locus Coeruleus, Protein Bodies, Electron microscopy, Parkinson's disease, Chromogranin A, Vesicular Monoamine Transporter-2, immunogold postembedding electron microscopy

Conference: 4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014.

Presentation Type: Poster presentation

Topic: morphological and functional characterizations

Citation: Kloukina I, Havaki S and Chrysanthou-Piterou M (2014). Amine-storing Organelles in Soma and Dendrites of Human Locus Coeruleus Neurons. Front. Syst. Neurosci. Conference Abstract: 4th NAMASEN Training Workshop - Dendrites 2014. doi: 10.3389/conf.fnsys.2014.05.00033

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Received: 11 Apr 2014; Published Online: 12 Jun 2014.

* Correspondence: Dr. Ismini Kloukina, Th. Th. Cozzika Foundation, Neurobiology Research Institute, Athens, Greece, isminik@aol.com