Evidence map›Paper›PMID 26954758›Full record

ArticlePloS one2016

Silencing Status Epilepticus-Induced BDNF Expression with Herpes Simplex Virus Type-1 Based Amplicon Vectors.

Chiara Falcicchia, Pascal Trempat, Anna Binaschi, Coline Perrier-Biollay, Paolo Roncon, Marie Soukupova, Hervé Berthommé, Michele Simonato

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Gene Therapy Tools for Brain Diseases.Frontiers in pharmacology · 2019
    Review
  5. Personalized Needles for Microinjections in the Rodent Brain.Journal of visualized experiments : JoVE · 2018
    Article
  6. New Tools for Epilepsy Therapy.Frontiers in cellular neuroscience · 2018
    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

8 authors at 2 institutions in 2 countries.

Chiara FalcicchiaDepartment of Medical Science, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
Pascal TrempatDepartment of Medical Science, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
Anna BinaschiDepartment of Medical Science, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
Coline Perrier-BiollayBioviron, Université Claude Bernard Lyon 1, Villeurbanne, France.
Paolo RonconDepartment of Medical Science, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
Marie SoukupovaDepartment of Medical Science, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
Hervé BerthomméBioviron, Université Claude Bernard Lyon 1, Villeurbanne, France.
Michele SimonatoDepartment of Medical Science, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
University of Ferrara · ITUniversité Claude Bernard Lyon 1 · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brain-derived neurotrophic factor (BDNF) has been found to produce pro- but also anti-epileptic effects. Thus, its validity as a therapeutic target must be verified using advanced tools designed to block or to enhance its signal. The aim of this study was to develop tools to silence the BDNF signal. We generated Herpes simplex virus type 1 (HSV-1) derived amplicon vectors, i.e. viral particles containing a genome of 152 kb constituted of concatameric repetitions of an expression cassette, enabling the expression of the gene of interest in multiple copies. HSV-1 based amplicon vectors are non-pathogenic and have been successfully employed in the past for gene delivery into the brain of living animals. Therefore, amplicon vectors should represent a logical choice for expressing a silencing cassette, which, in multiple copies, is expected to lead to an efficient knock-down of the target gene expression. Here, we employed two amplicon-based BDNF silencing strategies. The first, antisense, has been chosen to target and degrade the cytoplasmic mRNA pool of BDNF, whereas the second, based on the convergent transcription technology, has been chosen to repress transcription at the BDNF gene. Both these amplicon vectors proved to be effective in down-regulating BDNF expression in vitro, in BDNF-expressing mesoangioblast cells. However, only the antisense strategy was effective in vivo, after inoculation in the hippocampus in a model of status epilepticus in which BDNF mRNA levels are strongly increased. Interestingly, the knocking down of BDNF levels induced with BDNF-antisense was sufficient to produce significant behavioral effects, in spite of the fact that it was produced only in a part of a single hippocampus. In conclusion, this study demonstrates a reliable effect of amplicon vectors in knocking down gene expression in vitro and in vivo. Therefore, this approach may find broad applications in neurobiological studies.

Indexed as

Gene ExpressionGene SilencingAnimalsBehavior, AnimalBrain-Derived Neurotrophic FactorCell Line, TumorChlorocebus aethiopsDisease Models, AnimalDNA, AntisenseGene OrderGenetic VectorsGene Transfer TechniquesHerpesvirus 1, HumanHippocampusHumansMaleBrain-Derived Neurotrophic FactorDNA, Antisense

Identifiers

PMID26954758
PMCPMC4783051
OpenAlexW2295741860

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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.