Evidence map›Paper›PMID 38934107›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

The ketamine metabolite (2R,6R)-hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer's disease.

Felipe C Ribeiro, Danielle Cozachenco, Elentina K Argyrousi, Agnieszka Staniszewski, Shane Wiebe, Joao D Calixtro, Rubens Soares-Neto, Aycheh Al-Chami, Fatema El Sayegh, Sara Bermudez and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

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

13 citing papers in PubMed.

  1. Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026
    Review
  2. Article
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  5. A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
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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

21 authors.

Felipe C RibeiroInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Danielle CozachencoInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Elentina K ArgyrousiTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Agnieszka StaniszewskiTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Shane WiebeDepartment of Biochemistry, McGill University, Montreal, Quebec, Canada.
Joao D CalixtroInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Rubens Soares-NetoInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Aycheh Al-ChamiDepartment of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Fatema El SayeghDepartment of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Sara BermudezDepartment of Biochemistry, McGill University, Montreal, Quebec, Canada.
Emily ArsenaultDepartment of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Marcelo CossenzaDepartment of Physiology and Pharmacology, Fluminense Federal University, Biomedical Institute, Niterói, Rio de Janeiro, Brazil.
Jean-Claude LacailleDepartment of Neurosciences, Université de Montréal, Centre for Interdisciplinary Research on Brain and Learning and Research Group on Neural Signaling and Circuits, Montreal, Quebec, Canada.
Karim NaderDepartment of Psychology, McGill University, Montreal, Quebec, Canada.
Hongyu SunDepartment of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Fernanda G De FeliceInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Mychael V LourencoInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Ottavio ArancioTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Argel Aguilar-VallesDepartment of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Nahum SonenbergDepartment of Biochemistry, McGill University, Montreal, Quebec, Canada.
Sergio T FerreiraInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Funding

SUMOylation and Amyloid-beta elevationR01NS049442 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARANCIO, OTTAVIO · 2005 to 2015
$4.1M
Alzheimer's Association AARF-21-848798Alzheimer's Society CanadaBlas Frangione Early Career Achievement Award NIH-NINDS/R01NS049442Conselho Nacional de Desenvolvimento Científico e TecnológicoFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroInstituto Nacional Saúde Cerebral 406020/2022-1International Brain Research OrganizationNational Institute of Translational NeuroscienceNINDS NIH HHS R01 NS049442Serrapilheira Institute R-2012-37967
6 · The paper itself

Abstract

introductionImpaired brain protein synthesis, synaptic plasticity, and memory are major hallmarks of Alzheimer's disease (AD). The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to modulate protein synthesis, but its effects on memory in AD models remain elusive.

methodsWe investigated the effects of HNK on hippocampal protein synthesis, long-term potentiation (LTP), and memory in AD mouse models.

resultsHNK activated extracellular signal-regulated kinase 1/2 (ERK1/2), mechanistic target of rapamycin (mTOR), and p70S6 kinase 1 (S6K1)/ribosomal protein S6 signaling pathways. Treatment with HNK rescued hippocampal LTP and memory deficits in amyloid-β oligomers (AβO)-infused mice in an ERK1/2-dependent manner. Treatment with HNK further corrected aberrant transcription, LTP and memory in aged APP/PS1 mice. DISCUSSION: Our findings demonstrate that HNK induces signaling and transcriptional responses that correct synaptic and memory deficits in AD mice. These results raise the prospect that HNK could serve as a therapeutic approach in AD. HIGHLIGHTS: The ketamine metabolite HNK activates hippocampal ERK/mTOR/S6 signaling pathways. HNK corrects hippocampal synaptic and memory defects in two mouse models of AD. Rescue of synaptic and memory impairments by HNK depends on ERK signaling. HNK corrects aberrant transcriptional signatures in APP/PS1 mice.

Indexed as

Alzheimer DiseaseDisease Models, AnimalHippocampusKetamineMice, TransgenicNeuronal PlasticityAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsHumansLong-Term PotentiationMaleMemoryMemory DisordersMiceMice, Inbred C57BL6-hydroxynorketamineAmyloid beta-PeptidesAmyloid beta-Protein PrecursorKetaminePresenilin-1RNA, MessengerTOR Serine-Threonine KinasesAlzheimer's diseasehydroxynorketaminememorymRNA translationsynaptic plasticity

Identifiers

PMID38934107
PMCPMC11350050

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Registered trials

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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.