Abstract
Hyposmia is an early symptom of idiopathic Parkinson’s disease but the pathological bases of such dysfunction are largely unknown. The distribution of α-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by α-synucleinopathy were investigated in the olfactory system in Parkinson’s disease. Immunohistochemical distribution of α-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. α-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 α-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 α-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 α-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.
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Abbreviations
- ACC:
-
Nucleus accumbens
- AON:
-
Anterior olfactory nucleus
- AONb:
-
Bulbar anterior olfactory nucleus
- AONcal:
-
Cortical anterior lateral anterior olfactory nucleus
- AONcam:
-
Cortical anterior medial anterior olfactory nucleus
- AONpal:
-
Cortical posterior lateral anterior olfactory nucleus
- AONcpm:
-
Cortical posterior medial anterior olfactory nucleus
- AONi:
-
Intrapeduncular anterior olfactory nucleus
- AONr:
-
Retrobulbar anterior olfactory nucleus
- BL:
-
Basolateral amygdala
- BM:
-
Basomedial amygdala
- CB:
-
Calbindin
- Ce:
-
Central amydala
- CR:
-
Calretinin
- EC:
-
Entorhinal cortex
- EPL:
-
External plexiform layer
- GL:
-
Glomerular layer
- GCL:
-
Granule cell layer
- IPD:
-
Idiopathic Parkinson’s disease
- Me:
-
Medial amgydala
- MOB:
-
Main olfactory bulb
- molf:
-
Medial olfactory radiation
- NT:
-
Neurotrace
- olfr:
-
Olfactory radiation
- ONL:
-
Outer nerve layer
- OP:
-
Olfactory peduncle
- ot:
-
Olfactory tract
- PAC:
-
Periamygdaloid cortex
- PD:
-
Parkinson’s disease
- Pir:
-
Piriform cortex
- PMOL:
-
Posteromedial orbital lobule
- PV:
-
Parvalbumin
- S:
-
Subiculum
- SA:
-
Stratum album
- SG:
-
Straight gyrus
- SMT:
-
Somatostatin
- SP:
-
Substance P
- SYN:
-
α-Synuclein
- TH:
-
Tyrosine hydroxylase
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Acknowledgments
The tissue was obtained from the Banc de Teixits Neurològics, Univ. Barcelona-Hospital Clínic and from the Banco de Tejidos/Fundación para investigaciones neurológicas, Univ. Complutense de Madrid. The authors thank members of LNH. International Science Editing revised the English version of the manuscript. The authors are indebted to Dr. Mimi Halpern for reading and commenting on the manuscript. Supported by the Autonomous Government of Castilla-La Mancha/FEDER [grants PI-2006/15 and PCC08-0064]. Authors declare no conflict of interests. This work is part of the Doctoral Thesis of Isabel Úbeda-Bañón.
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Ubeda-Bañon, I., Saiz-Sanchez, D., de la Rosa-Prieto, C. et al. α-Synucleinopathy in the human olfactory system in Parkinson’s disease: involvement of calcium-binding protein- and substance P-positive cells. Acta Neuropathol 119, 723–735 (2010). https://doi.org/10.1007/s00401-010-0687-9
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DOI: https://doi.org/10.1007/s00401-010-0687-9