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Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity
S Y Chen1, A Periasamy, B Yang
1Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, 27599-7090, USA.
Abstract:
Neural crest cells (NCCs) have been identified as an important target population relative to ethanol-induced teratogenicity in both mouse and avian models. Additionally, whole embryo culture mouse models have shown strain-related differences in sensitivity to ethanol-induced damage following acute exposure during early NCC development. That differential sensitivity of NCCs may contribute to these strain differences has been unexplored. For this purpose, cultured NCCs from an inbred mouse strain (C57BL/6J; C57) that is more sensitive to ethanol-induced teratogenicity than an outbred strain (ICR) were compared. This study showed that the incidence of cell death was significantly higher for the C57 NCCs than those from the ICR strain at all ethanol concentrations tested, and as early as 12 hours after initial exposure to 100 mM ethanol. The lateral mobility of the membrane lipids was faster and the membrane GM1 content was lower in C57 cells than ICR cells both under control conditions and at all doses and times tested. Ethanol exposure resulted in significant increases in the membrane lipid lateral mobility, and decreases in the membrane GM1 content that occurred in a dose and time-dependent manner in the NCCs from both strains. A significant correlation was found between the GM1 content and lateral mobility of the membrane lipids, the lateral mobility of membrane lipids and cell viability, as well as the GM1 content and cell viability in the NCCs from both strains. These results suggest that different strain sensitivities to ethanol-induced teratogencity may lie, at least in part, in the interstrain differential response of the NCC population and that the vulnerability of the NCCs to ethanol-induced death may be related to their endogenous membrane GM1 content.
Insights
Mouse strain differences in ethanol sensitivity may stem from neural crest cells (NCCs). C57BL/6J NCCs showed higher cell death and altered membrane properties compared to ICR NCCs after ethanol exposure.
Area of Science:
- Developmental biology
- Neuroscience
- Toxicology
Background:
- Neural crest cells (NCCs) are sensitive to ethanol-induced teratogenicity.
- Mouse models exhibit strain-related differences in ethanol sensitivity during early NCC development.
- The role of NCCs in these strain differences remains unclear.
Purpose of the Study:
- To investigate if differential NCC sensitivity contributes to strain differences in ethanol teratogenicity.
- To compare ethanol's effects on NCCs from sensitive (C57BL/6J) and less sensitive (ICR) mouse strains.
Main Methods:
- Primary NCC cultures from C57BL/6J and ICR mice were exposed to ethanol.
- Cell death incidence, membrane lipid lateral mobility, and GM1 ganglioside content were assessed.
- Correlations between membrane properties and cell viability were analyzed.
Main Results:
- C57BL/6J NCCs exhibited significantly higher cell death than ICR NCCs at all tested ethanol concentrations.
- Ethanol exposure increased lipid lateral mobility and decreased GM1 content in NCCs from both strains in a dose- and time-dependent manner.
- Significant correlations were found between GM1 content, lipid mobility, and cell viability.
Conclusions:
- Interstrain differences in NCC response to ethanol contribute to varying teratogenicity sensitivity.
- NCC vulnerability to ethanol-induced death is linked to endogenous membrane GM1 content and lipid dynamics.