Evidence map›Paper›PMID 31122677›Full record

ArticleNeuron2019

Loss of Adaptive Myelination Contributes to Methotrexate Chemotherapy-Related Cognitive Impairment.

Anna C Geraghty, Erin M Gibson, Reem A Ghanem, Jacob J Greene, Alfonso Ocampo, Andrea K Goldstein, Lijun Ni, Tao Yang, Rebecca M Marton, Sergiu P Paşca and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 1 pooled it
22.5field-weighted citation impact, top 1% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 1 synthesis or guideline pooled it, 272 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
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  8. Review
  9. Article
  10. Review
  11. Cancer treatment-related cognitive impairment.Neuro-oncology advances · 2026
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Senolytic treatment induces oligodendrocyte dysfunction and demyelination in the corpus callosum.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Anna C GeraghtyDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Erin M GibsonDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Reem A GhanemDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Jacob J GreeneDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Alfonso OcampoDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Andrea K GoldsteinDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Lijun NiDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Tao YangDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Rebecca M MartonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
Sergiu P PaşcaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
Michael E GreenbergDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Frank M LongoDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Michelle MonjeDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: mmonje@stanford.edu.
Stanford University · USCalifornia Institute for Regenerative Medicine · USHarvard University · US

Funding

Glioma Circuitry: Bridging Systems Neuroscience and CancerDP1NS111132 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2018 to 2022
$5.7M
Neuronal activity-regulated mechanisms of glioma growthR01NS092597 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2016 to 2021
$2.1M
NINDS NIH HHS DP1 NS111132NINDS NIH HHS R01 NS092597
6 · The paper itself

Abstract

Activity-dependent myelination is thought to contribute to adaptive neurological function. However, the mechanisms by which activity regulates myelination and the extent to which myelin plasticity contributes to non-motor cognitive functions remain incompletely understood. Using a mouse model of chemotherapy-related cognitive impairment (CRCI), we recently demonstrated that methotrexate (MTX) chemotherapy induces complex glial dysfunction for which microglial activation is central. Here, we demonstrate that remote MTX exposure blocks activity-regulated myelination. MTX decreases cortical Bdnf expression, which is restored by microglial depletion. Bdnf-TrkB signaling is a required component of activity-dependent myelination. Oligodendrocyte precursor cell (OPC)-specific TrkB deletion in chemotherapy-naive mice results in impaired cognitive behavioral performance. A small-molecule TrkB agonist rescues both myelination and cognitive impairment after MTX chemotherapy. This rescue after MTX depends on intact TrkB expression in OPCs. Taken together, these findings demonstrate a molecular mechanism required for adaptive myelination that is aberrant in CRCI due to microglial activation.

Indexed as

AnimalsBrain-Derived Neurotrophic FactorCerebral CortexChannelrhodopsinsCognition DisordersDisease Models, AnimalHumansImmunosuppressive AgentsLuminescent ProteinsMembrane GlycoproteinsMethotrexateMiceMice, Inbred C57BLMice, TransgenicMyelin SheathOligodendrocyte Precursor Cells1-(3-dimethylaminopropyl)-3-ethylureaBrain-Derived Neurotrophic FactorChannelrhodopsinsImmunosuppressive AgentsLuminescent ProteinsMembrane GlycoproteinsMethotrexateNtrk2 protein, mouseOrganic ChemicalsPLX5622Protein-Tyrosine KinasesReceptor, trkBUreaadaptive myelinationBDNFchemotherapy-related cognitive impairmentmyelinmyelin plasticityoligodendrocyteoligodendrocyte precursor cellTrkB

Identifiers

PMID31122677
PMCPMC6697075
OpenAlexW2946168453

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.