Akeju O, Davis-Dusenbery BN, Cassel SH, Ichida JK, Eggan K. Ketamine exposure in early development impairs specification of the primary germ cell layers. Neurotoxicology and teratology. 43:59-68. Pubmed: 24746641 DOI:S0892-0362(14)00040-3


Preclinical and clinical evidence implicates N-methyl-d-aspartate receptor (NMDAr) signaling in early embryological development. However, the role of NMDAr signaling in early development has not been well studied. Here, we use a mouse embryonic stem cell model to perform a step-wise exploration of the effects of NMDAr signaling on early cell fate specification. We found that antagonism of the NMDAr impaired specification into the neuroectodermal and mesoendodermal cell lineages, with little or no effect on specification of the extraembryonic endoderm cell lineage. Consistent with these findings, exogenous NMDA promoted neuroectodermal differentiation. Finally, NMDAr antagonism modified expression of several key targets of TGF-β superfamily signaling, suggesting a mechanism for these findings. In summary, this study shows that NMDAr antagonism interferes with the normal developmental pathways of embryogenesis, and suggests that interference is most pronounced prior to neuroectodermal and mesoendodermal cell fate specification.
Copyright © 2014 Elsevier Inc. All rights reserved.

Related Faculty

Photo of Kevin Eggan

Kevin Eggan investigates the mechanisms that cause motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS), and seeks to translate new discoveries into new therapeutic options for patients.

Search Menu