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:	Katarína Tiklová, Linda Gillberg, Nikolaos Volakakis, Hilda Lundén-Miguel, Lina Dahl, Geidy E. Serrano, Charles H. Adler, Thomas G. Beach, Thomas Perlmann
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Parkinson’s disease gene expression RNA sequencing disease duration neurodegenerative disease cell death Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/2688c8e2113b4db987bfcd1c61b338d9
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spelling	oai:doaj.org-article:2688c8e2113b4db987bfcd1c61b338d92021-11-11T15:28:24ZDisease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients1662-509910.3389/fnmol.2021.763777https://doaj.org/article/2688c8e2113b4db987bfcd1c61b338d92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.763777/fullhttps://doaj.org/toc/1662-5099Analyses 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.Katarína TiklováKatarína TiklováLinda GillbergLinda GillbergNikolaos VolakakisHilda Lundén-MiguelLina DahlGeidy E. SerranoCharles H. AdlerThomas G. BeachThomas PerlmannFrontiers Media S.A.articleParkinson’s diseasegene expressionRNA sequencingdisease durationneurodegenerative diseasecell deathNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson’s disease gene expression RNA sequencing disease duration neurodegenerative disease cell death Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Parkinson’s disease gene expression RNA sequencing disease duration neurodegenerative disease cell death Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Katarína Tiklová Katarína Tiklová Linda Gillberg Linda Gillberg Nikolaos Volakakis Hilda Lundén-Miguel Lina Dahl Geidy E. Serrano Charles H. Adler Thomas G. Beach Thomas Perlmann Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients
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.
format	article
author	Katarína Tiklová Katarína Tiklová Linda Gillberg Linda Gillberg Nikolaos Volakakis Hilda Lundén-Miguel Lina Dahl Geidy E. Serrano Charles H. Adler Thomas G. Beach Thomas Perlmann
author_facet	Katarína Tiklová Katarína Tiklová Linda Gillberg Linda Gillberg Nikolaos Volakakis Hilda Lundén-Miguel Lina Dahl Geidy E. Serrano Charles H. Adler Thomas G. Beach Thomas Perlmann
author_sort	Katarína Tiklová
title	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_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_sort	disease duration influences gene expression in neuromelanin-positive cells from parkinson’s disease patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2688c8e2113b4db987bfcd1c61b338d9
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Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients

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