Ketamine exposure in early development impairs specification of the primary germ cell layers

被引：8

作者：

Akeju, Oluwaseun ^{[1
,2
]}

Davis-Dusenbery, Brandi N. ^{[2
]}

Cassel, Seth H. ^{[2
]}

Ichida, Justin K. ^{[2
]}

Eggan, Kevin ^{[2
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA

[2] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Howard Hughes Med Inst, Cambridge, MA 02138 USA

来源：

NEUROTOXICOLOGY AND TERATOLOGY | 2014年 / 43卷

基金：

美国国家卫生研究院;

关键词：

Mouse embryonic stem cells; NMDA; Ketamine; Neurogenesis; Mesoendoderm; Differentiation; EMBRYONIC STEM-CELLS; ANTERIOR-POSTERIOR POLARITY; VISCERAL ENDODERM; NEURAL CONVERSION; GENE-EXPRESSION; MOTOR-NEURONS; AXIS; DIFFERENTIATION; EPIBLAST; NEUROTOXICITY;

D O I：

10.1016/j.ntt.2014.04.001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Preclinical and clinical evidence implicates N-methyl-D-aspartate receptor (NMDAr) signaling in early embryo-logical 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-beta 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. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：59 / 68

页数：10

共 49 条

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Selective inactivation of Otx2 mRNA isoforms reveals isoform-specific requirement for visceral endoderm anteriorization and head morphogenesis and highlights cell diversity in the visceral endoderm [J].