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The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy

The Brain-Derived Neurotrophic Factor is one of the most important trophic proteins in the brain. The role of this growth factor in neuronal plasticity, in health and disease, has been extensively studied. However, mechanisms of epigenetic regulation of Bdnf gene expression in epilepsy are still elu...

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Autores principales: Skupien-Jaroszek, Anna, Walczak, Agnieszka, Czaban, Iwona, Pels, Katarzyna Karolina, Szczepankiewicz, Andrzej Antoni, Krawczyk, Katarzyna, Ruszczycki, Błażej, Wilczynski, Grzegorz Marek, Dzwonek, Joanna, Magalska, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177504/
https://www.ncbi.nlm.nih.gov/pubmed/34086671
http://dx.doi.org/10.1371/journal.pone.0239111
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author Skupien-Jaroszek, Anna
Walczak, Agnieszka
Czaban, Iwona
Pels, Katarzyna Karolina
Szczepankiewicz, Andrzej Antoni
Krawczyk, Katarzyna
Ruszczycki, Błażej
Wilczynski, Grzegorz Marek
Dzwonek, Joanna
Magalska, Adriana
author_facet Skupien-Jaroszek, Anna
Walczak, Agnieszka
Czaban, Iwona
Pels, Katarzyna Karolina
Szczepankiewicz, Andrzej Antoni
Krawczyk, Katarzyna
Ruszczycki, Błażej
Wilczynski, Grzegorz Marek
Dzwonek, Joanna
Magalska, Adriana
author_sort Skupien-Jaroszek, Anna
collection PubMed
description The Brain-Derived Neurotrophic Factor is one of the most important trophic proteins in the brain. The role of this growth factor in neuronal plasticity, in health and disease, has been extensively studied. However, mechanisms of epigenetic regulation of Bdnf gene expression in epilepsy are still elusive. In our previous work, using a rat model of neuronal activation upon kainate-induced seizures, we observed a repositioning of Bdnf alleles from the nuclear periphery towards the nuclear center. This change of Bdnf intranuclear position was associated with transcriptional gene activity. In the present study, using the same neuronal activation model, we analyzed the relation between the percentage of the Bdnf allele at the nuclear periphery and clinical and morphological traits of epilepsy. We observed that the decrease of the percentage of the Bdnf allele at the nuclear periphery correlates with stronger mossy fiber sprouting—an aberrant form of excitatory circuits formation. Moreover, using in vitro hippocampal cultures we showed that Bdnf repositioning is a consequence of transcriptional activity. Inhibition of RNA polymerase II activity in primary cultured neurons with Actinomycin D completely blocked Bdnf gene transcription and repositioning occurring after neuronal excitation. Interestingly, we observed that histone deacetylases inhibition with Trichostatin A induced a slight increase of Bdnf gene transcription and its repositioning even in the absence of neuronal excitation. Presented results provide novel insight into the role of BDNF in epileptogenesis. Moreover, they strengthen the statement that this particular gene is a good candidate to search for a new generation of antiepileptic therapies.
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spelling pubmed-81775042021-06-07 The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy Skupien-Jaroszek, Anna Walczak, Agnieszka Czaban, Iwona Pels, Katarzyna Karolina Szczepankiewicz, Andrzej Antoni Krawczyk, Katarzyna Ruszczycki, Błażej Wilczynski, Grzegorz Marek Dzwonek, Joanna Magalska, Adriana PLoS One Research Article The Brain-Derived Neurotrophic Factor is one of the most important trophic proteins in the brain. The role of this growth factor in neuronal plasticity, in health and disease, has been extensively studied. However, mechanisms of epigenetic regulation of Bdnf gene expression in epilepsy are still elusive. In our previous work, using a rat model of neuronal activation upon kainate-induced seizures, we observed a repositioning of Bdnf alleles from the nuclear periphery towards the nuclear center. This change of Bdnf intranuclear position was associated with transcriptional gene activity. In the present study, using the same neuronal activation model, we analyzed the relation between the percentage of the Bdnf allele at the nuclear periphery and clinical and morphological traits of epilepsy. We observed that the decrease of the percentage of the Bdnf allele at the nuclear periphery correlates with stronger mossy fiber sprouting—an aberrant form of excitatory circuits formation. Moreover, using in vitro hippocampal cultures we showed that Bdnf repositioning is a consequence of transcriptional activity. Inhibition of RNA polymerase II activity in primary cultured neurons with Actinomycin D completely blocked Bdnf gene transcription and repositioning occurring after neuronal excitation. Interestingly, we observed that histone deacetylases inhibition with Trichostatin A induced a slight increase of Bdnf gene transcription and its repositioning even in the absence of neuronal excitation. Presented results provide novel insight into the role of BDNF in epileptogenesis. Moreover, they strengthen the statement that this particular gene is a good candidate to search for a new generation of antiepileptic therapies. Public Library of Science 2021-06-04 /pmc/articles/PMC8177504/ /pubmed/34086671 http://dx.doi.org/10.1371/journal.pone.0239111 Text en © 2021 Skupien-Jaroszek et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Skupien-Jaroszek, Anna
Walczak, Agnieszka
Czaban, Iwona
Pels, Katarzyna Karolina
Szczepankiewicz, Andrzej Antoni
Krawczyk, Katarzyna
Ruszczycki, Błażej
Wilczynski, Grzegorz Marek
Dzwonek, Joanna
Magalska, Adriana
The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
title The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
title_full The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
title_fullStr The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
title_full_unstemmed The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
title_short The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
title_sort interplay of seizures-induced axonal sprouting and transcription-dependent bdnf repositioning in the model of temporal lobe epilepsy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177504/
https://www.ncbi.nlm.nih.gov/pubmed/34086671
http://dx.doi.org/10.1371/journal.pone.0239111
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