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Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus
Synucleinopathies (including α-synucleinopathies), which include Parkinson’s disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the p...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723292/ https://www.ncbi.nlm.nih.gov/pubmed/29259548 http://dx.doi.org/10.3389/fnana.2017.00113 |
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author | Ubeda-Bañon, Isabel Flores-Cuadrado, Alicia Saiz-Sanchez, Daniel Martinez-Marcos, Alino |
author_facet | Ubeda-Bañon, Isabel Flores-Cuadrado, Alicia Saiz-Sanchez, Daniel Martinez-Marcos, Alino |
author_sort | Ubeda-Bañon, Isabel |
collection | PubMed |
description | Synucleinopathies (including α-synucleinopathies), which include Parkinson’s disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the partial loss of the sense of smell. The neural basis of hyposmia in PD, however, is poorly understood; but the AON appears to be a key structure in the disease’s progression. We analyzed whether α-synuclein was involved in the differential interneuron vulnerability associated with PD in the retrobulbar, cortical anterior and cortical posterior divisions of the AON. First, we determined the expression of the calcium binding interneuron markers, calretinin, calbindin and parvalbumin, as well as non-calcium binding interneuron marker, somatostatin, in neuronal cell bodies alone (cells/mm(2)) and in neuronal cell bodies and neurites (% of area fraction) of post-mortem tissue from PD cases and age-matched controls (n = 4 for each) by immunofluorescent confocal microscopy. Results indicated that parvalbumin expression was upregulated in neuronal cell bodies throughout the anterior olfactory nucleus of PD cases compared with controls. Furthermore, there was increased calbindin, calretinin and parvalbumin expression in the cell bodies and neurites of neurons in the retrobulbar division and also increased parvalbumin expression in the neurites of neurons in the cortical division; calretinin expression was also increased in neuronal cell bodies and neurites in the cortical posterior division. Second, we analyzed the co-localization of the above markers with α-synuclein, with results indicating that α-synuclein co-localized with the calcium-binding proteins, but only partially with somatostatin. Taken together, these results indicate differential expression levels among different neural markers in the divisions of the AON in PD cases and point to several possibilities, among them: possible neuroprotective mechanisms of calcium-binding proteins against α-synuclein; and the differential involvement of somatostatin in α-synuclein-positive cell bodies and neurites. |
format | Online Article Text |
id | pubmed-5723292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57232922017-12-19 Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus Ubeda-Bañon, Isabel Flores-Cuadrado, Alicia Saiz-Sanchez, Daniel Martinez-Marcos, Alino Front Neuroanat Neuroscience Synucleinopathies (including α-synucleinopathies), which include Parkinson’s disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the partial loss of the sense of smell. The neural basis of hyposmia in PD, however, is poorly understood; but the AON appears to be a key structure in the disease’s progression. We analyzed whether α-synuclein was involved in the differential interneuron vulnerability associated with PD in the retrobulbar, cortical anterior and cortical posterior divisions of the AON. First, we determined the expression of the calcium binding interneuron markers, calretinin, calbindin and parvalbumin, as well as non-calcium binding interneuron marker, somatostatin, in neuronal cell bodies alone (cells/mm(2)) and in neuronal cell bodies and neurites (% of area fraction) of post-mortem tissue from PD cases and age-matched controls (n = 4 for each) by immunofluorescent confocal microscopy. Results indicated that parvalbumin expression was upregulated in neuronal cell bodies throughout the anterior olfactory nucleus of PD cases compared with controls. Furthermore, there was increased calbindin, calretinin and parvalbumin expression in the cell bodies and neurites of neurons in the retrobulbar division and also increased parvalbumin expression in the neurites of neurons in the cortical division; calretinin expression was also increased in neuronal cell bodies and neurites in the cortical posterior division. Second, we analyzed the co-localization of the above markers with α-synuclein, with results indicating that α-synuclein co-localized with the calcium-binding proteins, but only partially with somatostatin. Taken together, these results indicate differential expression levels among different neural markers in the divisions of the AON in PD cases and point to several possibilities, among them: possible neuroprotective mechanisms of calcium-binding proteins against α-synuclein; and the differential involvement of somatostatin in α-synuclein-positive cell bodies and neurites. Frontiers Media S.A. 2017-12-05 /pmc/articles/PMC5723292/ /pubmed/29259548 http://dx.doi.org/10.3389/fnana.2017.00113 Text en Copyright © 2017 Ubeda-Bañon, Flores-Cuadrado, Saiz-Sanchez and Martinez-Marcos. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Ubeda-Bañon, Isabel Flores-Cuadrado, Alicia Saiz-Sanchez, Daniel Martinez-Marcos, Alino Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus |
title | Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus |
title_full | Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus |
title_fullStr | Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus |
title_full_unstemmed | Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus |
title_short | Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus |
title_sort | differential effects of parkinson’s disease on interneuron subtypes within the human anterior olfactory nucleus |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723292/ https://www.ncbi.nlm.nih.gov/pubmed/29259548 http://dx.doi.org/10.3389/fnana.2017.00113 |
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