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Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients

Analyses of gene expression in cells affected by neurodegenerative disease can provide important insights into disease mechanisms and relevant stress response pathways. Major symptoms in Parkinson’s disease (PD) are caused by the degeneration of midbrain dopamine (mDA) neurons within the substantia...

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Autores principales: Tiklová, Katarína, Gillberg, Linda, Volakakis, Nikolaos, Lundén-Miguel, Hilda, Dahl, Lina, Serrano, Geidy E., Adler, Charles H., Beach, Thomas G., Perlmann, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632647/
https://www.ncbi.nlm.nih.gov/pubmed/34867188
http://dx.doi.org/10.3389/fnmol.2021.763777
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author Tiklová, Katarína
Gillberg, Linda
Volakakis, Nikolaos
Lundén-Miguel, Hilda
Dahl, Lina
Serrano, Geidy E.
Adler, Charles H.
Beach, Thomas G.
Perlmann, Thomas
author_facet Tiklová, Katarína
Gillberg, Linda
Volakakis, Nikolaos
Lundén-Miguel, Hilda
Dahl, Lina
Serrano, Geidy E.
Adler, Charles H.
Beach, Thomas G.
Perlmann, Thomas
author_sort Tiklová, Katarína
collection PubMed
description Analyses of gene expression in cells affected by neurodegenerative disease can provide important insights into disease mechanisms and relevant stress response pathways. Major symptoms in Parkinson’s disease (PD) are caused by the degeneration of midbrain dopamine (mDA) neurons within the substantia nigra. Here we isolated neuromelanin-positive dopamine neurons by laser capture microdissection from post-mortem human substantia nigra samples recovered at both early and advanced stages of PD. Neuromelanin-positive cells were also isolated from individuals with incidental Lewy body disease (ILBD) and from aged-matched controls. Isolated mDA neurons were subjected to genome-wide gene expression analysis by mRNA sequencing. The analysis identified hundreds of dysregulated genes in PD. Results showed that mostly non-overlapping genes were differentially expressed in ILBD, subjects who were early after diagnosis (less than five years) and those autopsied at more advanced stages of disease (over five years since diagnosis). The identity of differentially expressed genes suggested that more resilient, stably surviving DA neurons were enriched in samples from advanced stages of disease, either as a consequence of positive selection of a less vulnerable long-term surviving mDA neuron subtype or due to up-regulation of neuroprotective gene products.
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spelling pubmed-86326472021-12-02 Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients Tiklová, Katarína Gillberg, Linda Volakakis, Nikolaos Lundén-Miguel, Hilda Dahl, Lina Serrano, Geidy E. Adler, Charles H. Beach, Thomas G. Perlmann, Thomas Front Mol Neurosci Molecular Neuroscience Analyses of gene expression in cells affected by neurodegenerative disease can provide important insights into disease mechanisms and relevant stress response pathways. Major symptoms in Parkinson’s disease (PD) are caused by the degeneration of midbrain dopamine (mDA) neurons within the substantia nigra. Here we isolated neuromelanin-positive dopamine neurons by laser capture microdissection from post-mortem human substantia nigra samples recovered at both early and advanced stages of PD. Neuromelanin-positive cells were also isolated from individuals with incidental Lewy body disease (ILBD) and from aged-matched controls. Isolated mDA neurons were subjected to genome-wide gene expression analysis by mRNA sequencing. The analysis identified hundreds of dysregulated genes in PD. Results showed that mostly non-overlapping genes were differentially expressed in ILBD, subjects who were early after diagnosis (less than five years) and those autopsied at more advanced stages of disease (over five years since diagnosis). The identity of differentially expressed genes suggested that more resilient, stably surviving DA neurons were enriched in samples from advanced stages of disease, either as a consequence of positive selection of a less vulnerable long-term surviving mDA neuron subtype or due to up-regulation of neuroprotective gene products. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632647/ /pubmed/34867188 http://dx.doi.org/10.3389/fnmol.2021.763777 Text en Copyright © 2021 Tiklová, Gillberg, Volakakis, Lundén-Miguel, Dahl, Serrano, Adler, Beach and Perlmann. https://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) and the copyright owner(s) 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 Molecular Neuroscience
Tiklová, Katarína
Gillberg, Linda
Volakakis, Nikolaos
Lundén-Miguel, Hilda
Dahl, Lina
Serrano, Geidy E.
Adler, Charles H.
Beach, Thomas G.
Perlmann, Thomas
Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
title Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
title_full Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
title_fullStr Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
title_full_unstemmed Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
title_short Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
title_sort disease duration influences gene expression in neuromelanin-positive cells from parkinson’s disease patients
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632647/
https://www.ncbi.nlm.nih.gov/pubmed/34867188
http://dx.doi.org/10.3389/fnmol.2021.763777
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