NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects

Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tub...

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Detalles Bibliográficos
Autores: Sequerra, Eduardo Bouth, Goyal, Raman, Castro, Patricio A., Levin, Jacqueline B., Borodinsky, Laura N.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Brasil
Institución:Universidade Federal do Rio Grande do Norte (UFRN)
Repositorio:Repositório Institucional da UFRN
Idioma:inglés
OAI Identifier:oai:repositorio.ufrn.br:123456789/25139
Acceso en línea:https://repositorio.ufrn.br/jspui/handle/123456789/25139
Access Level:acceso abierto
Palabra clave:Neural Tube Defect
N-methyl-D-aspartate
Desenvolvimento
Plasticidade neural
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spelling NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defectsNeural Tube DefectN-methyl-D-aspartateDesenvolvimentoPlasticidade neuralFailure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that N-methyl-D-aspartate (NMDA) receptors are important for the formation of the neural tube and loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation.2018-10-302018-05-09T13:26:46Z2018-04-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfSEQUERRA, E. B. et al. NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects. J Neurosci., pii: 2634-17, abr./2018. DOI: 10.1523/JNEUROSCI.2634-17.2018https://repositorio.ufrn.br/jspui/handle/123456789/2513910.1523/JNEUROSCI.2634-17.2018ark:/41046/001300001jc9henginfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNSequerra, Eduardo BouthGoyal, RamanCastro, Patricio A.Levin, Jacqueline B.Borodinsky, Laura N.2025-05-29T17:19:57Zoai:repositorio.ufrn.br:123456789/25139Repositório InstitucionalPUBhttp://repositorio.ufrn.br/oai/repositorio@bczm.ufrn.bropendoar:2025-05-29T17:19:57Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.none.fl_str_mv NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
title NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
spellingShingle NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
Sequerra, Eduardo Bouth
Neural Tube Defect
N-methyl-D-aspartate
Desenvolvimento
Plasticidade neural
title_short NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
title_full NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
title_fullStr NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
title_full_unstemmed NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
title_sort NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects
dc.creator.none.fl_str_mv Sequerra, Eduardo Bouth
Goyal, Raman
Castro, Patricio A.
Levin, Jacqueline B.
Borodinsky, Laura N.
author Sequerra, Eduardo Bouth
author_facet Sequerra, Eduardo Bouth
Goyal, Raman
Castro, Patricio A.
Levin, Jacqueline B.
Borodinsky, Laura N.
author_role author
author2 Goyal, Raman
Castro, Patricio A.
Levin, Jacqueline B.
Borodinsky, Laura N.
author2_role author
author
author
author
dc.subject.por.fl_str_mv Neural Tube Defect
N-methyl-D-aspartate
Desenvolvimento
Plasticidade neural
topic Neural Tube Defect
N-methyl-D-aspartate
Desenvolvimento
Plasticidade neural
description Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that N-methyl-D-aspartate (NMDA) receptors are important for the formation of the neural tube and loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation.
publishDate 2018
dc.date.none.fl_str_mv 2018-05-09T13:26:46Z
2018-04-30
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv SEQUERRA, E. B. et al. NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects. J Neurosci., pii: 2634-17, abr./2018. DOI: 10.1523/JNEUROSCI.2634-17.2018
https://repositorio.ufrn.br/jspui/handle/123456789/25139
10.1523/JNEUROSCI.2634-17.2018
dc.identifier.dark.fl_str_mv ark:/41046/001300001jc9h
identifier_str_mv SEQUERRA, E. B. et al. NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects. J Neurosci., pii: 2634-17, abr./2018. DOI: 10.1523/JNEUROSCI.2634-17.2018
10.1523/JNEUROSCI.2634-17.2018
ark:/41046/001300001jc9h
url https://repositorio.ufrn.br/jspui/handle/123456789/25139
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFRN
instname:Universidade Federal do Rio Grande do Norte (UFRN)
instacron:UFRN
instname_str Universidade Federal do Rio Grande do Norte (UFRN)
instacron_str UFRN
institution UFRN
reponame_str Repositório Institucional da UFRN
collection Repositório Institucional da UFRN
repository.name.fl_str_mv Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)
repository.mail.fl_str_mv repositorio@bczm.ufrn.br
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score 15,301603

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