Evidence map›Paper›PMID 32087004›Full record

ArticleAging cell2020

miR-181a negatively modulates synaptic plasticity in hippocampal cultures and its inhibition rescues memory deficits in a mouse model of Alzheimer's disease.

Carlos J Rodriguez-Ortiz, Gilberto Aleph Prieto, Alessandra C Martini, Stefania Forner, Laura Trujillo-Estrada, Frank M LaFerla, David Baglietto-Vargas, Carl W Cotman, Masashi Kitazawa

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

Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.8field-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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. MicroRNAs and synaptic dysfunction in Parkinson's disease.Molecular therapy. Nucleic acids · 2025
    Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
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 2 countries.

Carlos J Rodriguez-OrtizDepartment of Medicine, University of California, Irvine, California.ORCID 0000-0003-2688-947X
Gilberto Aleph PrietoInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
Alessandra C MartiniInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
Stefania FornerInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
Laura Trujillo-EstradaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
Frank M LaFerlaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
David Baglietto-VargasInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
Carl W CotmanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
Masashi KitazawaDepartment of Medicine, University of California, Irvine, California.
University of California, Irvine · US

Funding

TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Epigenetic suppression of histone methylation reverses age and AD-related cognitive declineRF1AG057558 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI WOOD, MARCELO ANDRES · 2018 to 2018
$3.8M
Exercise-induced epigenetic mechanisms underlying neuronal plasticity and cognitionR01AG051807 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI COTMAN, CARL WAYNE, WOOD, MARCELO ANDRES · 2016 to 2020
$3.1M
Environmental copper exposure and its impact on microglial Abeta clearanceR01ES024331 · NIEHS · UNIVERSITY OF CALIFORNIA, MERCED · PI KITAZAWA, MASASHI · 2014 to 2018
$2.7M
NIA NIH HHS P01 AG000538NIA NIH HHS R01 AG051807NIA NIH HHS RF1 AG057558NIEHS NIH HHS R01 ES024331NIH HHS AG00538NIH HHS ES024331NIH HHS P01-AG000538NIH HHS R01AG051807NIH HHS RF1AG057558
6 · The paper itself

Abstract

MicroRNAs play a pivotal role in rapid, dynamic, and spatiotemporal modulation of synaptic functions. Among them, recent emerging evidence highlights that microRNA-181a (miR-181a) is particularly abundant in hippocampal neurons and controls the expression of key plasticity-related proteins at synapses. We have previously demonstrated that miR-181a was upregulated in the hippocampus of a mouse model of Alzheimer's disease (AD) and correlated with reduced levels of plasticity-related proteins. Here, we further investigated the underlying mechanisms by which miR-181a negatively modulated synaptic plasticity and memory. In primary hippocampal cultures, we found that an activity-dependent upregulation of the microRNA-regulating protein, translin, correlated with reduction of miR-181a upon chemical long-term potentiation (cLTP), which induced upregulation of GluA2, a predicted target for miR-181a, and other plasticity-related proteins. Additionally, Aβ treatment inhibited cLTP-dependent induction of translin and subsequent reduction of miR-181a, and cotreatment with miR-181a antagomir effectively reversed the effects elicited by Aβ but did not rescue translin levels, suggesting that the activity-dependent upregulation of translin was upstream of miR-181a. In mice, a learning episode markedly decreased miR-181a in the hippocampus and raised the protein levels of GluA2. Lastly, we observed that inhibition of miR-181a alleviated memory deficits and increased GluA2 and GluA1 levels, without restoring translin, in the 3xTg-AD model. Taken together, our results indicate that miR-181a is a major negative regulator of the cellular events that underlie synaptic plasticity and memory through AMPA receptors, and importantly, Aβ disrupts this process by suppressing translin and leads to synaptic dysfunction and memory impairments in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCells, CulturedDisease Models, AnimalDNA-Binding ProteinsHippocampusLearningLong-Term PotentiationMaleMemoryMemory DisordersMiceMice, Inbred C57BLMicroRNAsNeuronsAmyloid beta-PeptidesDNA-Binding Proteinsglutamate receptor ionotropic, AMPA 2MicroRNAsmirn181 microRNA, mouseReceptors, AMPARNA-Binding ProteinsTsn protein, mouseAMPA receptoramyloid-beta oligomersGluA2long-term potentiationmicroRNAsspatial memorytranslin/trax

Identifiers

PMID32087004
PMCPMC7059142
OpenAlexW3008609356

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.