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SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the bidirectional transport of lipids, such as cholesterol and vitamin E, between these particles and cells. During early development, SR-BI is expressed in extraembryonic tissue, specifically in trophoblast giant cells in the parietal yolk sac. We previously showed that approximately 50% of SR-BI−/− embryos fail to close the anterior neural tube and develop exencephaly, a perinatal lethal condition. Here, we evaluated the role of SR-BI in embryonic vitamin E uptake during murine neural tube closure. Our results showed that SR-BI−/− embryos had a very low vitamin E content in comparison to SR-BI+/+ embryos. Whereas SR-BI−/− embryos with closed neural tubes (nSR-BI−/−) had high levels of reactive oxygen species (ROS), intermediate ROS levels between SR-BI+/+ and nSR-BI−/− embryos were detected in SR-BI−/− with NTD (NTD SR-BI−/−). Reduced expression of Pax3, Alx1 and Alx3 genes was found in NTD SR-BI−/− embryos. Maternal α-tocopherol dietary supplementation prevented NTD almost completely (from 54% to 2%, p −/− embryos and normalized ROS and gene expression levels. In sum, our results suggest the involvement of SR-BI in the maternal provision of embryonic vitamin E to the mouse embryo during neural tube closure.

The axon initial segment (AIS) is the site of initiation of action potentials and also influences action potential waveform, firing pattern and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12 - 60 μm) and diameters (0.2 - 0.8 μm), and an average of 50% reduction in diameter between their widest and thinnest parts. Ultrastructural analysis revealed submembranous localization of Ank-G at nodes of Ranvier and AIS. Serial ultrathin section analysis and 3D reconstructions revealed that Ank-G colocalized with TH only at the AIS. Few cases of synaptic innervation of the AIS of dopaminergic neurons were observed. mRNA in situ hybridization of brain-specific Nav subunits revealed the expression of Nav1.2 by most SNc neurons and a small proportion expressing Nav1.6. The presence of sodium channels, along with the submembranous location of Ank-G is consistent with the role of AIS in action potential generation. Differences in the size of the AIS likely underlie differences in firing pattern, while the tapering diameter of AIS may define a trigger zone for action potentials. Finally, the conspicuous expression of Nav1.2 by the majority of dopaminergic neurons may explain their high threshold for firing and their low discharge rate. This article is protected by copyright. All rights reserved.