Gene expression analysis of the cerebellar cortex in essential tremor.

Cerebellar Cortex / metabolism Databases, Genetic Essential Tremor / genetics Female Follow-Up Studies Gene Expression Gene Regulatory Networks / physiology Humans Male Prospective Studies Sequence Analysis, RNA / methods
Cerebellum Essential tremor Gene set enrichment analysis Purkinje cell RNA-seq String networks

Journal

Neuroscience letters
ISSN: 1872-7972
Titre abrégé: Neurosci Lett
Pays: Ireland
ID NLM: 7600130

Informations de publication

Date de publication:
16 03 2020
Historique:
received: 02 07 2019
revised: 28 09 2019
accepted: 08 10 2019
pubmed: 11 11 2019
medline: 20 4 2021
entrez: 11 11 2019
Statut: ppublish

Résumé

Essential tremor (ET) is one of the most common neurological diseases, with a central feature of an 8-12 Hz kinetic tremor. While previous postmortem studies have identified a cluster of morphological changes in the ET cerebellum centered in/around the Purkinje cell (PC) population, including a loss of PCs in some studies, the underlying molecular mechanisms for these changes are not clear. As genomic studies of ET patients have yet to identify major genetic contributors and animal models that fully recapitulate the human disease do not yet exist, the study of human tissue is currently the most applicable method to gain a mechanistic insight into ET disease pathogenesis. To begin exploration of an underlying molecular source of ET disease pathogenesis, we have performed the first transcriptomic analysis by direct sequencing of RNA from frozen cerebellar cortex tissue in 33 ET patients compared to 21 normal controls. Principal component analysis showed a heterogenous distribution of the expression data in ET patients that only partially overlapped with control patients. Differential expression analysis identified 231 differentially expressed gene transcripts ('top gene hits'), a subset of which has defined expression profiles in the cerebellum across neuronal and glial cell types but a largely unknown relationship to cerebellar function and/or ET pathogenesis. Gene set enrichment analysis (GSEA) identified dysregulated pathways of interest and stratified dysregulation among ET cases. By GSEA and mining curated databases, we compiled major categories of dysregulated processes and clustered string networks of known interacting proteins. Here we demonstrate that these 'top gene hits' contribute to regulation of four main biological processes, which are 1) axon guidance, 2) microtubule motor activity, 3) endoplasmic reticulum (ER) to Golgi transport and 4) calcium signaling/synaptic transmission. The results of our transcriptomic analysis suggest there is a range of different processes involved among ET cases, and draws attention to a particular set of genes and regulatory pathways that provide an initial platform to further explore the underlying biology of ET.

Identifiants

DOI: 10.1016/j.neulet.2019.134540 PMID: 31707044 PMC: PMC7593093
pubmed: 31707044
pii: S0304-3940(19)30643-3
doi: 10.1016/j.neulet.2019.134540
pmc: PMC7593093
mid: NIHMS1549307
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

134540

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS088257
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

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Auteurs

Regina T Martuscello (RT)

Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, P&S 15-405, New York, NY, USA; College of Physicians and Surgeons, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, New York, NY, USA. Electronic address: rm3419@cumc.columbia.edu.

Chloë A Kerridge (CA)

Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, P&S 15-405, New York, NY, USA; College of Physicians and Surgeons, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, New York, NY, USA. Electronic address: chloe.kerridge@gmail.com.

Debotri Chatterjee (D)

Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, P&S 15-405, New York, NY, USA; College of Physicians and Surgeons, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, New York, NY, USA. Electronic address: dc679@cornell.edu.

Whitney G Hartstone (WG)

Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, P&S 15-405, New York, NY, USA; College of Physicians and Surgeons, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, New York, NY, USA. Electronic address: wgh2109@cumc.columbia.edu.

Sheng-Han Kuo (SH)

College of Physicians and Surgeons, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, BB302, New York, NY, USA. Electronic address: sk3295@cumc.columbia.edu.

Peter A Sims (PA)

Department of Neurology, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, BB302, New York, NY, USA; Department of Systems Biology, Columbia University Medical Center, 3960 Broadway, RM208, New York, NY, USA; Sulzberger Columbia Genome Center, Columbia University Medical Center, 1150 St. Nicholas Ave., New York, NY, USA; Department of Biochemistry & Molecular Biophysics, Columbia University Medical Center, 701 W 168th Street, New York, NY, USA. Electronic address: pas2182@cumc.columbia.edu.

Elan D Louis (ED)

Department of Neurology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT, USA; Department of Chronic Disease Epidemiology, Yale School of Public Health, 15 York Street, Yale University, New Haven, CT, USA; Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT, USA. Electronic address: elan.louis@yale.edu.

Phyllis L Faust (PL)

Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, P&S 15-405, New York, NY, USA; College of Physicians and Surgeons, Columbia University Medical Center and the New York Presbyterian Hospital, 630 W 168th Street, New York, NY, USA. Electronic address: plf3@cumc.columbia.edu.

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Classifications MeSH

questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Tronc cérébral › Rhombencéphale › Métencéphale › Cervelet › Cortex cérébelleux › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Bases de données comme sujet › Bases de données factuelles › Bases de données génétiques › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Troubles de la motricité › Tremblement essentiel › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études de suivi › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › Réseaux de régulation génique › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Gene expression analysis of the cerebellar...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Gene expression analysis of the cerebellar...