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Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice

BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is pathologically characterized by loss of dopaminergic neurons from the substantia nigra, the presence of aggregated α-synuclein (αS) and evidence of neuroinflammation. Experimental studies have shown that the cer...

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Autores principales: Rutherford, Nicola J., Sacino, Amanda N., Brooks, Mieu, Ceballos-Diaz, Carolina, Ladd, Thomas B., Howard, Jasie K., Golde, Todd E., Giasson, Benoit I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520273/
https://www.ncbi.nlm.nih.gov/pubmed/26223783
http://dx.doi.org/10.1186/s13024-015-0029-4
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author Rutherford, Nicola J.
Sacino, Amanda N.
Brooks, Mieu
Ceballos-Diaz, Carolina
Ladd, Thomas B.
Howard, Jasie K.
Golde, Todd E.
Giasson, Benoit I.
author_facet Rutherford, Nicola J.
Sacino, Amanda N.
Brooks, Mieu
Ceballos-Diaz, Carolina
Ladd, Thomas B.
Howard, Jasie K.
Golde, Todd E.
Giasson, Benoit I.
author_sort Rutherford, Nicola J.
collection PubMed
description BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is pathologically characterized by loss of dopaminergic neurons from the substantia nigra, the presence of aggregated α-synuclein (αS) and evidence of neuroinflammation. Experimental studies have shown that the cerebral injection of recombinant fibrillar αS, especially in αS transgenic mouse models, can induce the formation and spread of αS inclusion pathology. However, studies reporting this phenomenon did not consider the presence of lipopolysaccharide (LPS) in the injected αS, produced in E. coli, as a potential confound. The objectives of this study are to develop a method to remove the LPS contamination and investigate the differences in pathologies induced by αS containing LPS or αS highly purified of LPS. RESULTS AND CONCLUSIONS: We were able to remove >99.5 % of the LPS contamination from the αS preparations through the addition of a cation exchange step during purification. The αS pathology induced by injection of fibrils produced from αS containing LPS or purified of LPS, showed a similar distribution pattern; however, there was less spread into the cortex of the mice injected with αS containing higher levels of LPS. As previously reported, injection of αS fibrils could induce astrogliosis, and αS inclusions were present within astrocytes in mice injected with fibrils comprised of αS with or without cation exchange purification. Furthermore, we identified the presence of αS pathology in ependymal cells in both groups of mice, which suggests the involvement of a novel mechanism for spread in this model of αS pathology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-015-0029-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-45202732015-07-31 Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice Rutherford, Nicola J. Sacino, Amanda N. Brooks, Mieu Ceballos-Diaz, Carolina Ladd, Thomas B. Howard, Jasie K. Golde, Todd E. Giasson, Benoit I. Mol Neurodegener Research Article BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is pathologically characterized by loss of dopaminergic neurons from the substantia nigra, the presence of aggregated α-synuclein (αS) and evidence of neuroinflammation. Experimental studies have shown that the cerebral injection of recombinant fibrillar αS, especially in αS transgenic mouse models, can induce the formation and spread of αS inclusion pathology. However, studies reporting this phenomenon did not consider the presence of lipopolysaccharide (LPS) in the injected αS, produced in E. coli, as a potential confound. The objectives of this study are to develop a method to remove the LPS contamination and investigate the differences in pathologies induced by αS containing LPS or αS highly purified of LPS. RESULTS AND CONCLUSIONS: We were able to remove >99.5 % of the LPS contamination from the αS preparations through the addition of a cation exchange step during purification. The αS pathology induced by injection of fibrils produced from αS containing LPS or purified of LPS, showed a similar distribution pattern; however, there was less spread into the cortex of the mice injected with αS containing higher levels of LPS. As previously reported, injection of αS fibrils could induce astrogliosis, and αS inclusions were present within astrocytes in mice injected with fibrils comprised of αS with or without cation exchange purification. Furthermore, we identified the presence of αS pathology in ependymal cells in both groups of mice, which suggests the involvement of a novel mechanism for spread in this model of αS pathology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-015-0029-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-30 /pmc/articles/PMC4520273/ /pubmed/26223783 http://dx.doi.org/10.1186/s13024-015-0029-4 Text en © Rutherford et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rutherford, Nicola J.
Sacino, Amanda N.
Brooks, Mieu
Ceballos-Diaz, Carolina
Ladd, Thomas B.
Howard, Jasie K.
Golde, Todd E.
Giasson, Benoit I.
Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
title Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
title_full Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
title_fullStr Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
title_full_unstemmed Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
title_short Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
title_sort studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520273/
https://www.ncbi.nlm.nih.gov/pubmed/26223783
http://dx.doi.org/10.1186/s13024-015-0029-4
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