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

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Abstract

Olfactory deficits are an early feature of Parkinson’s disease (PD). Neuropathologically, α-synucleinopathy (Lewy bodies and neurites) is observed earlier (stage 1) in the olfactory system than in the substantia nigra (stage 3), and this could underlies the early olfactory symptoms. In the present report, we analyzed the distribution of α-synuclein deposits in tertiary olfactory structures (anterior olfactory nucleus, olfactory tubercle, piriform cortex, posterolateral cortical amygdala and lateral entorhinal cortex) of homozygous transgenic mice (aged 2–8 months) overexpressing the human A53T variant of α-synuclein. To address the hypothesis of progressive α-synucleinopathy within the olfactory system, the distribution of α-synuclein was analyzed in conjunction with tracer injections into the main olfactory bulb. The time-course of α-synuclein expression revealed a significant increase in the piriform cortex at the age of 8 months compared to other brain structures. Tracing experiments revealed that olfactory projections are reduced in homozygous as compared to wild type animals. Double-labeling experiments show labeled axonal collaterals of mitral cells entering layer II of the piriform cortex in close proximity to α-synuclein-positive cells. To our knowledge, this is the first study addressing the progression of α-synuclein expression in a vulnerable neuronal pathway in PD.

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Acknowledgments

This study was supported by the Spanish Ministry of Science and Innovation (BFU2010-15729) and the Autonomous Government of Castilla-La Mancha-FEDER (PEIC11-0045-4490). The authors would like to thank the laboratory of Dr. Calvo for their assistance in genotyping animals. The English version of this manuscript was corrected by International Science Editing. This work constitutes part of the Doctoral Thesis of Isabel Úbeda-Bañón.

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  1. 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

    Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, Carlos de la Rosa-Prieto & Alino Martinez-Marcos

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  1. Isabel Ubeda-Bañon
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  2. Daniel Saiz-Sanchez
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  3. Carlos de la Rosa-Prieto
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  4. Alino Martinez-Marcos
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Correspondence to Alino Martinez-Marcos.

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Ubeda-Bañon, I., Saiz-Sanchez, D., de la Rosa-Prieto, C. et al. α-Synuclein in the olfactory system of a mouse model of Parkinson’s disease: correlation with olfactory projections. Brain Struct Funct 217, 447–458 (2012). https://doi.org/10.1007/s00429-011-0347-4

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