Evidence map›Paper›PMID 21181126›Full record

ArticlePsychopharmacology2011

Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy.

Laura Lyons, Maha ElBeltagy, Jariya Umka, Rachel Markwick, Carla Startin, Geoffrey Bennett, Peter Wigmore

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

Article in Psychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Modulation of premotor cortex response to sequence motor learning during escitalopram intake.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
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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

7 authors at 6 institutions in 4 countries.

Laura LyonsSchool of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK. mbxll@nottingham.ac.uk
Maha ElBeltagy
Jariya Umka
Rachel Markwick
Carla Startin
Geoffrey Bennett
Peter Wigmore
Queen's Medical Centre · GBKhon Kaen University · THMenoufia University · EGUniversity College London · GBUniversity of Birmingham · GBUniversity of Nottingham · GB

Funding

Cancer Research UK
6 · The paper itself

Abstract

rationaleAdjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment.

objectivesThe present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine.

methodsMale Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified.

resultsMTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers.

conclusionsThese results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors.

Indexed as

Administration, OralAnimalsAntimetabolites, AntineoplasticBehavior, AnimalCell ProliferationCell SurvivalFluoxetineHippocampusInjections, IntravenousMaleMemory DisordersMemory, Short-TermMethotrexateNeuroprotective AgentsRatsRats, Inbred StrainsAntimetabolites, AntineoplasticFluoxetineMethotrexateNeuroprotective Agents

Identifiers

PMID21181126
PMCPMC3072503
OpenAlexW2010548227

What OpenQuestion holds

Textmetadata
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.