Evidence map›Paper›PMID 40110982›Full record

ArticleSleep2025

Enduring non-rapid eye movement sleep fragmentation following methotrexate chemotherapy in cancer-naïve mice.

Leah Boyd, Adrian Berisha, Adrian M Gomez, Erin M Gibson, Jeremy C Borniger

Abstract read
In one paragraph

Article in Sleep, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

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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

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Leah BoydCold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Adrian BerishaCold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Adrian M GomezCold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Erin M GibsonDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
Jeremy C BornigerCold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.ORCID 0000-0002-5419-0271

Funding

Central mechanisms of glucocorticoid circadian rhythm dysfunction in breast cancerR01CA286651 · NCI · COLD SPRING HARBOR LABORATORY · PI Jeremy Borniger · 2024 to 2026
$2.3M
Circadian regulation of cancer therapy-associated neuroinflammationR21CA267135 · NCI · STANFORD UNIVERSITY · PI VALDEZ, ERIN G · 2022 to 2023
$417k
Cancer Center Support Grant 5P30CA045508-36NCI NIH HHS R21 CA267135NIH-NCI R01CA286651
6 · The paper itself

Abstract

STUDY

objectivesSleep disruption is common in people with cancer and survivors, but understanding the mechanisms driving these problems is difficult due to heterogeneity among cancers, patients, and treatment modalities. We investigated whether the common antifolate chemotherapeutic agent methotrexate (MTX) promotes changes in sleep independent of cancer in adult mice.

methodsAdult mice (>7 weeks old, both sexes, n = 13) were exposed to either a clinically relevant chemotherapy regimen with methotrexate (n = 7) or saline (control, n = 6) accompanied by continuous EEG/EMG telemetry recording. Sleep states were scored as either wake, non-rapid eye movement (NREM) sleep, or REM sleep in 5-second epochs weekly during MTX or saline treatment and then 2 weeks following the last injection to examine enduring changes in sleep-wake cycles.

resultsMTX exposure caused NREM sleep fragmentation, indicated by (1) shorter and more frequent NREM sleep bouts, (2) more transitions between wake and NREM sleep, and (3) more accumulated NREM sleep bouts over time. These effects were first detected after the second MTX injection and lasted into the 2-week follow-up recording. MTX did not alter delta power in NREM sleep, indicating no changes to sleep quality. The total time spent in each vigilance state remained unaffected by MTX use. Finally, when given MTX, male mice displayed more fragmented sleep compared to female mice.

conclusionsMethotrexate promotes NREM sleep fragmentation, without affecting sleep quality or time spent asleep. This effect is stronger in males. These data suggest that chemotherapy can cause long-term sleep disruption independent of cancer presence.

Indexed as

Antimetabolites, AntineoplasticMethotrexateSleep DeprivationSleep StagesAnimalsElectroencephalographyElectromyographyFemaleMaleMiceMice, Inbred C57BLAntimetabolites, AntineoplasticMethotrexatecancerchemotherapymethotrexatesleep fragmentationsleep quality

Identifiers

PMID40110982
PMCPMC12361856

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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.