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

Eduardo B. Sequerra, Raman Goyal, Patricio A. Castro, Jacqueline B. Levin, Laura N Borodinsky

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 NMDA receptors are important for the formation of the neural tube and that the 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.

Original languageEnglish (US)
Pages (from-to)4762-4773
Number of pages12
JournalJournal of Neuroscience
Volume38
Issue number20
DOIs
StatePublished - May 16 2018

Fingerprint

Neural Tube
Neural Tube Defects
N-Methyl-D-Aspartate Receptors
Anticonvulsants
Neural Plate
Glutamic Acid
Xenopus laevis
Valproic Acid
Cell Movement
Cell Proliferation
Calcium
Pregnancy
DNA
Incidence

Keywords

  • Birth defects
  • Calcium dynamics
  • Epilepsy
  • Glutamate signaling
  • Neural plate
  • Valproic acid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects. / Sequerra, Eduardo B.; Goyal, Raman; Castro, Patricio A.; Levin, Jacqueline B.; Borodinsky, Laura N.

In: Journal of Neuroscience, Vol. 38, No. 20, 16.05.2018, p. 4762-4773.

Research output: Contribution to journalArticle

Sequerra, Eduardo B. ; Goyal, Raman ; Castro, Patricio A. ; Levin, Jacqueline B. ; Borodinsky, Laura N. / NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 20. pp. 4762-4773.
@article{8ffedb17e33642c6b69f8ddca10fcf6b,
title = "NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects",
abstract = "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 NMDA receptors are important for the formation of the neural tube and that the 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.",
keywords = "Birth defects, Calcium dynamics, Epilepsy, Glutamate signaling, Neural plate, Valproic acid",
author = "Sequerra, {Eduardo B.} and Raman Goyal and Castro, {Patricio A.} and Levin, {Jacqueline B.} and Borodinsky, {Laura N}",
year = "2018",
month = "5",
day = "16",
doi = "10.1523/JNEUROSCI.2634-17.2018",
language = "English (US)",
volume = "38",
pages = "4762--4773",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "20",

}

TY - JOUR

T1 - NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects

AU - Sequerra, Eduardo B.

AU - Goyal, Raman

AU - Castro, Patricio A.

AU - Levin, Jacqueline B.

AU - Borodinsky, Laura N

PY - 2018/5/16

Y1 - 2018/5/16

N2 - 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 NMDA receptors are important for the formation of the neural tube and that the 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.

AB - 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 NMDA receptors are important for the formation of the neural tube and that the 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.

KW - Birth defects

KW - Calcium dynamics

KW - Epilepsy

KW - Glutamate signaling

KW - Neural plate

KW - Valproic acid

UR - http://www.scopus.com/inward/record.url?scp=85050937414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050937414&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2634-17.2018

DO - 10.1523/JNEUROSCI.2634-17.2018

M3 - Article

C2 - 29712790

AN - SCOPUS:85050937414

VL - 38

SP - 4762

EP - 4773

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 20

ER -