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

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High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity. / Verschuuren, Marlies; Verstraelen, Peter; Garcia-Diaz Barriga, Gerardo; Cilissen, Ines; Coninx, Emma; Verslegers, Mieke; Larsen, Peter; Nuydens, Rony; De Vos, Winnok H.

In: Acta Neuropathologica Communications, Vol. 7, No. 93, 04.06.2019, p. 1-16.

Research output: Contribution to journalArticle

Harvard

Verschuuren, M, Verstraelen, P, Garcia-Diaz Barriga, G, Cilissen, I, Coninx, E, Verslegers, M, Larsen, P, Nuydens, R & De Vos, WH 2019, 'High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity', Acta Neuropathologica Communications, vol. 7, no. 93, pp. 1-16. https://doi.org/10.1186/s40478-019-0741-3

APA

Verschuuren, M., Verstraelen, P., Garcia-Diaz Barriga, G., Cilissen, I., Coninx, E., Verslegers, M., ... De Vos, W. H. (2019). High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity. Acta Neuropathologica Communications, 7(93), 1-16. https://doi.org/10.1186/s40478-019-0741-3

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Verschuuren, Marlies ; Verstraelen, Peter ; Garcia-Diaz Barriga, Gerardo ; Cilissen, Ines ; Coninx, Emma ; Verslegers, Mieke ; Larsen, Peter ; Nuydens, Rony ; De Vos, Winnok H. / High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity. In: Acta Neuropathologica Communications. 2019 ; Vol. 7, No. 93. pp. 1-16.

Bibtex - Download

@article{3405572eea5045a6893c5ec8687610e9,
title = "High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity",
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.",
keywords = "Neuronal connectivity, Neuronal network, Synapse, Calcium imaging, High-content screening, Neurodegeneration, Antioxidant depletion, hTau.P301L",
author = "Marlies Verschuuren and Peter Verstraelen and {Garcia-Diaz Barriga}, Gerardo and Ines Cilissen and Emma Coninx and Mieke Verslegers and Peter Larsen and Rony Nuydens and {De Vos}, {Winnok H.}",
note = "Score=10",
year = "2019",
month = "6",
day = "4",
doi = "10.1186/s40478-019-0741-3",
language = "English",
volume = "7",
pages = "1--16",
journal = "Acta Neuropathologica Communications",
issn = "2051-5960",
publisher = "Springer Verlag",
number = "93",

}

RIS - Download

TY - JOUR

T1 - High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity

AU - Verschuuren, Marlies

AU - Verstraelen, Peter

AU - Garcia-Diaz Barriga, Gerardo

AU - Cilissen, Ines

AU - Coninx, Emma

AU - Verslegers, Mieke

AU - Larsen, Peter

AU - Nuydens, Rony

AU - De Vos, Winnok H.

N1 - Score=10

PY - 2019/6/4

Y1 - 2019/6/4

N2 - 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.

AB - 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.

KW - Neuronal connectivity

KW - Neuronal network

KW - Synapse

KW - Calcium imaging

KW - High-content screening

KW - Neurodegeneration

KW - Antioxidant depletion

KW - hTau.P301L

UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/34630748

U2 - 10.1186/s40478-019-0741-3

DO - 10.1186/s40478-019-0741-3

M3 - Article

VL - 7

SP - 1

EP - 16

JO - Acta Neuropathologica Communications

JF - Acta Neuropathologica Communications

SN - 2051-5960

IS - 93

ER -

ID: 5322302