Evidence map›Paper›PMID 31040210›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis.

Rhonda R Voskuhl, Noriko Itoh, Alessia Tassoni, Macy Akiyo Matsukawa, Emily Ren, Vincent Tse, Ellis Jang, Timothy Takazo Suen, Yuichiro Itoh

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01466114 (A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis), which is not on this map. Cited by 112 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 2 pooled it
6.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01466114 phase2unknown statusnot on this map

A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis: Effect on Cognition.

TypeinterventionalSponsorUniversity of California, Los AngelesRan2011 to 2022Enrolled64ConditionsRelapsing-remitting Multiple Sclerosis, Secondary-progressive Multiple Sclerosis, Primary-progressive Multiple SclerosisArmsestriol, Placebo, Norethindrone, Progestin Placebo
3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 2 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Deletion ofBiology · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Deletion of the X-chromosomal geneScience translational medicine · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Spinal Cord Injury Remyelination: Pathways to Therapies.International journal of molecular sciences · 2025
    Review
  19. Review
  20. Article

52 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Rhonda R VoskuhlMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 rvoskuhl@mednet.ucla.edu.
Noriko ItohMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Alessia TassoniMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Macy Akiyo MatsukawaMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Emily RenMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Vincent TseMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Ellis JangMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Timothy Takazo SuenMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Yuichiro ItohMultiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
University of California, Los Angeles · US

Funding

Neuroprotection in MS: A Cell-Specific and Region-Specific Transcriptomics ApproachR01NS109670 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VOSKUHL, RHONDA R · 2018 to 2022
$2.2M
Parental imprinting of the X chromosome: effects on neurodegenerationR01NS096748 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VOSKUHL, RHONDA R · 2016 to 2020
$1.9M
NINDS NIH HHS R01 NS096748NINDS NIH HHS R01 NS109670
6 · The paper itself

Abstract

Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen-response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.

Indexed as

RemyelinationAnimalsCase-Control StudiesCholesterolCuprizoneEncephalomyelitis, Autoimmune, ExperimentalEstrogen Receptor betaFemaleGene ExpressionHomeostasisHumansMice, Inbred C57BLMiddle AgedMultiple SclerosisOligodendrogliaSequence Analysis, RNACholesterolCuprizoneEstrogen Receptor betacholesterolMS animal modelsmultiple sclerosisoligodendrocytesremyelination

Identifiers

PMID31040210
PMCPMC6525478
OpenAlexW2943340056

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.