Evidence map›Paper›PMID 29745864›Full record

ArticleBMC neuroscience2018

Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties.

Maria A Tikhonova, Tamara G Amstislavskaya, Victor M Belichenko, Larisa A Fedoseeva, Sergey P Kovalenko, Ekaterina E Pisareva, Alla S Avdeeva, Nataliya G Kolosova, Nikolai D Belyaev, Lyubomir I Aftanas

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

Article in BMC neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 28 citations in OpenAlex.

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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

10 authors at 4 institutions in 2 countries.

Maria A TikhonovaFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia. tikhonovama@physiol.ru.
Tamara G AmstislavskayaFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Victor M BelichenkoFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Larisa A FedoseevaFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Sergey P KovalenkoFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Ekaterina E PisarevaFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Alla S AvdeevaFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Nataliya G KolosovaFederal Research Center "Institute of Cytology and Genetics", Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
Nikolai D BelyaevUniversity of Leeds, Leeds, LS2 9JT, UK.
Lyubomir I AftanasFederal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Timakov St., 4, Novosibirsk, 630117, Russia.
Institute of Physiology and Basic Medicine · RUInstitute of Cytology and Genetics · RUNovosibirsk State University · RUUniversity of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe dominant hypothesis about the pathogenesis of Alzheimer's disease (AD) is the "amyloid cascade" concept and modulating the expression of proteins involved in the metabolism of amyloid-beta (Aβ) is proposed as an effective strategy for the prevention and therapy of AD. Recently, we found that an antibiotic ceftriaxone (CEF), which possesses neuroprotective activity, reduced cognitive deficits and neurodegenerative changes in OXYS rats, a model of sporadic AD. The molecular mechanisms of this effect are not completely clear, we suggested that the drug might serve as the regulator of the expression of the genes involved in the metabolism of Aβ and the pathogenesis of AD. The study was aimed to determine the effects of CEF on mRNA levels of Bace1 (encoding β-secretase BACE1 involved in Aβ production), Mme, Ide, Ece1, Ace2 (encoding enzymes involved in Aβ degradation), Epo (encoding erythropoietin related to endothelial function and clearance of Aβ across the blood brain barrier) in the frontal cortex, hippocampus, striatum, hypothalamus, and amygdala of OXYS and Wistar (control strain) male rats. Starting from the age of 14 weeks, animals received CEF (100 mg/kg/day, i.p., 36 days) or saline. mRNA levels were evaluated with RT-qPCR method. Biochemical parameters of plasma were measured for control of system effects of the treatment.

resultsTo better understand strain variations studied here, we compared the gene expression between untreated OXYS and Wistar rats. This comparison showed a significant decrease in mRNA levels of Ace2 in the frontal cortex and hypothalamus, and of Actb in the amygdala of untreated OXYS rats. Analysis of potential effects of CEF revealed its novel targets. In the compound-treated OXYS cohort, CEF diminished mRNA levels of Bace1 and Ace2 in the hypothalamus, and Aktb in the frontal cortex. Furthermore, CEF augmented Mme, Ide, and Epo mRNA levels in the amygdala as well as the levels of Ece1 and Aktb in the striatum. Finally, CEF also attenuated the activity of ALT and AST in plasma of OXYS rats.

conclusionThose findings disclosed novel targets for CEF action that might be involved into neuroprotective mechanisms at early, pre-plaque stages of AD-like pathology development.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainCeftriaxoneDisease Models, AnimalGene ExpressionMaleNeuroprotective AgentsRats, WistarRNA, MessengerAmyloid beta-PeptidesCeftriaxoneNeuroprotective AgentsRNA, MessengerAlzheimer’s diseaseAmyloid metabolismCeftriaxoneGene expressionmRNANeuroprotectionRats

Identifiers

PMID29745864
PMCPMC5998892
OpenAlexW2801633050

What Socratic 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 Socratic graph.