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:	Anna Skupien-Jaroszek, Agnieszka Walczak, Iwona Czaban, Katarzyna Karolina Pels, Andrzej Antoni Szczepankiewicz, Katarzyna Krawczyk, Błażej Ruszczycki, Grzegorz Marek Wilczynski, Joanna Dzwonek, Adriana Magalska
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d596a654b77a4c9c812038c27972a15b
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spelling	oai:doaj.org-article:d596a654b77a4c9c812038c27972a15b2021-12-02T20:03:57ZThe interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy.1932-620310.1371/journal.pone.0239111https://doaj.org/article/d596a654b77a4c9c812038c27972a15b2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0239111https://doaj.org/toc/1932-6203The 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.Anna Skupien-JaroszekAgnieszka WalczakIwona CzabanKatarzyna Karolina PelsAndrzej Antoni SzczepankiewiczKatarzyna KrawczykBłażej RuszczyckiGrzegorz Marek WilczynskiJoanna DzwonekAdriana MagalskaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0239111 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Skupien-Jaroszek Agnieszka Walczak Iwona Czaban Katarzyna Karolina Pels Andrzej Antoni Szczepankiewicz Katarzyna Krawczyk Błażej Ruszczycki Grzegorz Marek Wilczynski Joanna Dzwonek Adriana Magalska The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy.
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.
format	article
author	Anna Skupien-Jaroszek Agnieszka Walczak Iwona Czaban Katarzyna Karolina Pels Andrzej Antoni Szczepankiewicz Katarzyna Krawczyk Błażej Ruszczycki Grzegorz Marek Wilczynski Joanna Dzwonek Adriana Magalska
author_facet	Anna Skupien-Jaroszek Agnieszka Walczak Iwona Czaban Katarzyna Karolina Pels Andrzej Antoni Szczepankiewicz Katarzyna Krawczyk Błażej Ruszczycki Grzegorz Marek Wilczynski Joanna Dzwonek Adriana Magalska
author_sort	Anna Skupien-Jaroszek
title	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_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_sort	interplay of seizures-induced axonal sprouting and transcription-dependent bdnf repositioning in the model of temporal lobe epilepsy.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d596a654b77a4c9c812038c27972a15b
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The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy.

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