Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702.
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147.
Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E8919-E8928. doi: 10.1073/pnas.1808463115. Epub 2018 Sep 5.
Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in , owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase ()-null mutants and fail to encapsulate the neuronal cell bodies in the neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in mutants and leads to the PSE phenotype.
视觉刺激引起的癫痫发作（光敏性癫痫；PSE）是人类中常见的一种癫痫类型，但 PSE 背后的分子机制和遗传驱动因素尚不清楚，也尚未确定良好的遗传动物模型。在这里，我们展示了一种 PSE 的动物模型，其原因是皮层神经胶质缺陷。神经鞘磷脂合成酶 1（CerS1）表达缺陷的斑马鱼，其神经鞘磷脂（ceramide phosphocholine）合成相关的神经鞘氨醇磷酸乙醇胺合成酶（CerS）缺失突变体，皮层神经胶质的细胞膜严重受损，无法包裹神经元胞体。CerS1 合成的神经鞘氨醇，在 神经元皮层中，拯救了皮层神经胶质的异常和 PSE，这突显了这些脂质在神经胶质细胞膜中具有进化保守的作用。此外，我们还展示了导致 PSE 表型的 突变体中质膜结构的损伤，这导致了神经胶质细胞膜的崩溃。
