Evidence map›Paper›PMID 28143498›Full record

ArticleJournal of neuroinflammation2017

Neuroprotective effects of intrastriatal injection of rapamycin in a mouse model of excitotoxicity induced by quinolinic acid.

Soraya Wilke Saliba, Erica Leandro Marciano Vieira, Rebeca Priscila de Melo Santos, Eduardo Candelario-Jalil, Bernd L Fiebich, Luciene Bruno Vieira, Antonio Lucio Teixeira, Antonio Carlos Pinheiro de Oliveira

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 24% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

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  9. The Dephosphorylation of p70S6 (ThrNeurotoxicity research · 2020
    Article
  10. mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.International journal of molecular sciences · 2020
    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

8 authors at 3 institutions in 3 countries.

Soraya Wilke SalibaDepartment of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
Erica Leandro Marciano VieiraDepartment of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Rebeca Priscila de Melo SantosDepartment of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
Eduardo Candelario-JalilDepartment of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.
Bernd L FiebichDepartment of Psychiatry, University of Freiburg Medical School, Hauptstr. 5, 79104, Freiburg, Germany. bernd.fiebich@uniklinik-freiburg.de.
Luciene Bruno VieiraDepartment of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
Antonio Lucio TeixeiraDepartment of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Antonio Carlos Pinheiro de OliveiraDepartment of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil. antoniooliveira@icb.ufmg.br.
Universidade Federal de Minas Gerais · BRUniversity of Florida · USUniversity of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe mammalian target of rapamycin (mTOR) is a kinase involved in a variety of physiological and pathological functions. However, the exact role of mTOR in excitotoxicity is poorly understood. Here, we investigated the effects of mTOR inhibition with rapamycin against neurodegeneration, and motor impairment, as well as inflammatory profile caused by an excitotoxic stimulus.

methodsA single and unilateral striatal injection of quinolinic acid (QA) was used to induce excitotoxicity in mice. Rapamycin (250 nL of 0.2, 2, or 20 μM; intrastriatal route) was administered 15 min before QA injection. Forty-eight hours after QA administration, rotarod test was performed to evaluate motor coordination and balance. Fluoro-Jade C, Iba-1, and GFAP staining were used to evaluate neuronal cell death, microglia morphology, and astrocytes density, respectively, at this time point. Levels of cytokines and neurotrophic factors were measured by ELISA and Cytometric Bead Array 8 h after QA injection. Striatal synaptosomes were used to evaluate the release of glutamate.

resultsWe first demonstrated that rapamycin prevented the motor impairment induced by QA. Moreover, mTOR inhibition also reduced the neurodegeneration and the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α induced by excitotoxic stimulus. The lowest dose of rapamycin also increased the production of IL-10 and prevented the reduction of astrocyte density induced by QA. By using an in vitro approach, we demonstrated that rapamycin differently alters the release of glutamate from striatal synaptosomes induced by QA, reducing or enhancing the release of this neurotransmitter at low or high concentrations, respectively.

conclusionTaken together, these data demonstrated a protective effect of rapamycin against an excitotoxic stimulus. Therefore, this study provides new evidence of the detrimental role of mTOR in neurodegeneration, which might represent an important target for the treatment of neurodegenerative diseases.

Indexed as

AnimalsBody WeightCorpus StriatumCytokinesDisease Models, AnimalDose-Response Relationship, DrugGlutamic AcidMaleMiceMice, Inbred C57BLMovement DisordersNerve DegenerationNeurogliaNeuronsNeuroprotective AgentsNeurotoxicity SyndromesCytokinesGlutamic AcidNeuroprotective AgentsPotassium ChlorideQuinolinic AcidSirolimusGlutamateInflammationmTORNeurodegenerationNeurotrophic factorsQuinolinic acidRapamycin

Identifiers

PMID28143498
PMCPMC5282622
OpenAlexW2585753733

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.