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Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model

Metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to the neurotoxin MPP(+) in the brain causes permanent Parkinson’s disease-like symptoms by destroying dopaminergic neurons in the pars compacta of the substantia nigra in humans and non-human primates. However, the complete molecular...

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Autores principales: Kaya, Ibrahim, Nilsson, Anna, Luptáková, Dominika, He, Yachao, Vallianatou, Theodosia, Bjärterot, Patrik, Svenningsson, Per, Bezard, Erwan, Andrén, Per E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372136/
https://www.ncbi.nlm.nih.gov/pubmed/37495571
http://dx.doi.org/10.1038/s41531-023-00558-1
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author Kaya, Ibrahim
Nilsson, Anna
Luptáková, Dominika
He, Yachao
Vallianatou, Theodosia
Bjärterot, Patrik
Svenningsson, Per
Bezard, Erwan
Andrén, Per E.
author_facet Kaya, Ibrahim
Nilsson, Anna
Luptáková, Dominika
He, Yachao
Vallianatou, Theodosia
Bjärterot, Patrik
Svenningsson, Per
Bezard, Erwan
Andrén, Per E.
author_sort Kaya, Ibrahim
collection PubMed
description Metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to the neurotoxin MPP(+) in the brain causes permanent Parkinson’s disease-like symptoms by destroying dopaminergic neurons in the pars compacta of the substantia nigra in humans and non-human primates. However, the complete molecular pathology underlying MPTP-induced parkinsonism remains poorly understood. We used dual polarity matrix-assisted laser desorption/ionization mass spectrometry imaging to thoroughly image numerous glycerophospholipids and sphingolipids in coronal brain tissue sections of MPTP-lesioned and control non-human primate brains (Macaca mulatta). The results revealed specific distributions of several sulfatide lipid molecules based on chain-length, number of double bonds, and importantly, hydroxylation stage. More specifically, certain long-chain hydroxylated sulfatides with polyunsaturated chains in the molecular structure were depleted within motor-related brain regions in the MPTP-lesioned animals, e.g., external and internal segments of globus pallidus and substantia nigra pars reticulata. In contrast, certain long-chain non-hydroxylated sulfatides were found to be elevated within the same brain regions. These findings demonstrate region-specific dysregulation of sulfatide metabolism within the MPTP-lesioned macaque brain. The depletion of long-chain hydroxylated sulfatides in the MPTP-induced pathology indicates oxidative stress and oligodendrocyte/myelin damage within the pathologically relevant brain regions. Hence, the presented findings improve our current understanding of the molecular pathology of MPTP-induced parkinsonism within primate brains, and provide a basis for further research regarding the role of dysregulated sulfatide metabolism in PD.
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spelling pubmed-103721362023-07-28 Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model Kaya, Ibrahim Nilsson, Anna Luptáková, Dominika He, Yachao Vallianatou, Theodosia Bjärterot, Patrik Svenningsson, Per Bezard, Erwan Andrén, Per E. NPJ Parkinsons Dis Article Metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to the neurotoxin MPP(+) in the brain causes permanent Parkinson’s disease-like symptoms by destroying dopaminergic neurons in the pars compacta of the substantia nigra in humans and non-human primates. However, the complete molecular pathology underlying MPTP-induced parkinsonism remains poorly understood. We used dual polarity matrix-assisted laser desorption/ionization mass spectrometry imaging to thoroughly image numerous glycerophospholipids and sphingolipids in coronal brain tissue sections of MPTP-lesioned and control non-human primate brains (Macaca mulatta). The results revealed specific distributions of several sulfatide lipid molecules based on chain-length, number of double bonds, and importantly, hydroxylation stage. More specifically, certain long-chain hydroxylated sulfatides with polyunsaturated chains in the molecular structure were depleted within motor-related brain regions in the MPTP-lesioned animals, e.g., external and internal segments of globus pallidus and substantia nigra pars reticulata. In contrast, certain long-chain non-hydroxylated sulfatides were found to be elevated within the same brain regions. These findings demonstrate region-specific dysregulation of sulfatide metabolism within the MPTP-lesioned macaque brain. The depletion of long-chain hydroxylated sulfatides in the MPTP-induced pathology indicates oxidative stress and oligodendrocyte/myelin damage within the pathologically relevant brain regions. Hence, the presented findings improve our current understanding of the molecular pathology of MPTP-induced parkinsonism within primate brains, and provide a basis for further research regarding the role of dysregulated sulfatide metabolism in PD. Nature Publishing Group UK 2023-07-26 /pmc/articles/PMC10372136/ /pubmed/37495571 http://dx.doi.org/10.1038/s41531-023-00558-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kaya, Ibrahim
Nilsson, Anna
Luptáková, Dominika
He, Yachao
Vallianatou, Theodosia
Bjärterot, Patrik
Svenningsson, Per
Bezard, Erwan
Andrén, Per E.
Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model
title Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model
title_full Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model
title_fullStr Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model
title_full_unstemmed Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model
title_short Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson’s disease primate model
title_sort spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental mptp parkinson’s disease primate model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372136/
https://www.ncbi.nlm.nih.gov/pubmed/37495571
http://dx.doi.org/10.1038/s41531-023-00558-1
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