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 language | English (US) |
|---|---|
| Pages (from-to) | 4762-4773 |
| Number of pages | 12 |
| Journal | Journal of Neuroscience |
| Volume | 38 |
| Issue number | 20 |
| DOIs | |
| State | Published - May 16 2018 |
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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 journal › Article
}
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 -