α-Synucleinopathy in the human olfactory system in Parkinson’s disease: involvement of calcium-binding protein- and substance P-positive cells

Abstract

Hyposmia is an early symptom of idiopathic Parkinson's disease but the pathological bases of such dysfunction are largely unknown. The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. Immunohistochemical distribution of alpha-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson's disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. alpha-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by alpha-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that alpha-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by alpha-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.

α-Synuclein in the olfactory system of a mouse model of Parkinson’s disease: correlation with olfactory projections

“…These structures were selected for study for three reasons: (i) the secondary olfactory structure (the main olfactory bulb) was analyzed in a previous report (Ubeda-Banon et al 2010b); (ii) because severe involvement of secondary olfactory projection cells (i.e. mitral cells) was reported previously (Ubeda-Banon et al 2010b) it was interesting to analyze the a-synuclein distribution in tertiary olfactory structures for possible interrelationships; (iii) to permit comparison with human data (Braak et al 2003a;Hubbard et al 2007;Sengoku et al 2008;Silveira-Moriyama et al 2009;Ubeda-Banon et al 2010a) where tract-tracing experiments cannot be carried out.…”

“…Interestingly, neuropathological findings based on the detection of a-synuclein (Spillantini et al 1997) and ubiquitin (Daniel and Hawkes 1992;Pearce et al 1995) in Lewy bodies I. Ubeda-Bañon Á D. Saiz-Sanchez Á C. de la Rosa-Prieto Á A. Martinez-Marcos (&) Departamento de Ciencias Médicas, Facultad de Medicina de Ciudad Real, Laboratorio de Neuroplasticidad y Neurodegeneración, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avda. de Moledores s/n, 13071 Ciudad Real, Spain e-mail: Alino.Martinez@uclm.es indicate the involvement of specific nuclei in both the olfactory system (Hubbard et al 2007;Sengoku et al 2008;SilveiraMoriyama et al 2009;Ubeda-Banon et al 2010a) and the brainstem (the dorsal motor nuclei of the glossopharyngeal and vagal nerves) (Del Tredici et al 2002). In the olfactory system a-synuclein neuropathology is particularly prominent in the olfactory bulb and anterior olfactory nucleus (Braak et al 2003a).…”

The pathology roadmap in Parkinson disease

“…In the olfactory bulb, mitral cells exhibit Lewy pathology, but this is also seen in Alzheimer disease. 46,47 The anterior olfactory nucleus also shows Lewy pathology in incidental Lewy body disease. 12 The existence and targeting of neuronal loss in the olfactory system is controversial.…”

Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases

“…α-Synucleincalmodulin interaction accelerates fibrilization of synuclein, crucial for forming the core of Lewy bodies. α-Synuclein also colocalizes with other Ca 2+ -binding proteins, including calbindin and parvalbumin [115] , implicating the significance …”