Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

Post-mortem analysis of brains from Parkinson's disease (PD) patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn), which is known to be the main constituent of the agg...

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Autores principales:	Vanesa Sanchez-Guajardo, Fabia Febbraro, Deniz Kirik, Marina Romero-Ramos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c727cfbabca401197de48183975cf4f
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spelling	oai:doaj.org-article:2c727cfbabca401197de48183975cf4f2021-11-25T06:26:32ZMicroglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.1932-620310.1371/journal.pone.0008784https://doaj.org/article/2c727cfbabca401197de48183975cf4f2010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20098715/?tool=EBIhttps://doaj.org/toc/1932-6203Post-mortem analysis of brains from Parkinson's disease (PD) patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn), which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.Vanesa Sanchez-GuajardoFabia FebbraroDeniz KirikMarina Romero-RamosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8784 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vanesa Sanchez-Guajardo Fabia Febbraro Deniz Kirik Marina Romero-Ramos Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.
description	Post-mortem analysis of brains from Parkinson's disease (PD) patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn), which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.
format	article
author	Vanesa Sanchez-Guajardo Fabia Febbraro Deniz Kirik Marina Romero-Ramos
author_facet	Vanesa Sanchez-Guajardo Fabia Febbraro Deniz Kirik Marina Romero-Ramos
author_sort	Vanesa Sanchez-Guajardo
title	Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.
title_short	Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.
title_full	Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.
title_fullStr	Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.
title_full_unstemmed	Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.
title_sort	microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a raav based model of parkinson's disease.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/2c727cfbabca401197de48183975cf4f
work_keys_str_mv	AT vanesasanchezguajardo microgliaacquiredistinctactivationprofilesdependingonthedegreeofalphasynucleinneuropathologyinaraavbasedmodelofparkinsonsdisease AT fabiafebbraro microgliaacquiredistinctactivationprofilesdependingonthedegreeofalphasynucleinneuropathologyinaraavbasedmodelofparkinsonsdisease AT denizkirik microgliaacquiredistinctactivationprofilesdependingonthedegreeofalphasynucleinneuropathologyinaraavbasedmodelofparkinsonsdisease AT marinaromeroramos microgliaacquiredistinctactivationprofilesdependingonthedegreeofalphasynucleinneuropathologyinaraavbasedmodelofparkinsonsdisease
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Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

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