Evidence map›Paper›PMID 31164177›Full record

ArticleActa neuropathologica communications2019

High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity.

Marlies Verschuuren, Peter Verstraelen, Gerardo García-Díaz Barriga, Ines Cilissen, Emma Coninx, Mieke Verslegers, Peter H Larsen, Rony Nuydens, Winnok H De Vos

Erratum issuedAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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  11. A simple CaJournal of neuroscience methods · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Marlies VerschuurenLaboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Peter VerstraelenLaboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Gerardo García-Díaz BarrigaLaboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Ines CilissenLaboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Emma ConinxDepartment of Biology, Animal Physiology and Neurobiology, KU Leuven, Antwerp, Belgium.
Mieke VerslegersRadiobiology Unit, Institute of Environment, Health and Safety, Belgian Nuclear Research Centre, Mol, Belgium.
Peter H LarsenJanssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Rony NuydensJanssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Winnok H De VosLaboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium. winnok.devos@uantwerpen.be.ORCID 0000-0003-0960-6781

Funding

FWO 11ZF116NSAO 2017/0016VLAIO IWT150003
6 · The paper itself

Abstract

Therapeutic developments for neurodegenerative disorders are redirecting their focus to the mechanisms that contribute to neuronal connectivity and the loss thereof. Using a high-throughput microscopy pipeline that integrates morphological and functional measurements, we found that inhibition of dual leucine zipper kinase (DLK) increased neuronal connectivity in primary cortical cultures. This neuroprotective effect was not only observed in basal conditions but also in cultures depleted from antioxidants and in cultures in which microtubule stability was genetically perturbed. Based on the morphofunctional connectivity signature, we further showed that the effects were limited to a specific dose and time range. Thus, our results illustrate that profiling microscopy images with deep coverage enables sensitive interrogation of neuronal connectivity and allows exposing a pharmacological window for targeted treatments. In doing so, we revealed a broad-spectrum neuroprotective effect of DLK inhibition, which may have relevance to pathological conditions that ar.e associated with compromised neuronal connectivity.

Indexed as

AnimalsBrainCells, CulturedCerebral CortexHippocampusMAP Kinase Kinase KinasesMice, Inbred C57BLMicroscopyNeural PathwaysNeuronsNeuroprotective AgentsProtein Kinase InhibitorsMAP Kinase Kinase Kinasesmitogen-activated protein kinase kinase kinase 12Neuroprotective AgentsProtein Kinase InhibitorsAntioxidant depletionCalcium imagingHigh-content screeninghTau.P301LNeurodegenerationNeuronal connectivityNeuronal networkSynapse

Identifiers

PMID31164177
PMCPMC6549294

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.