Schwartz Nicholas U, Mileva Izolda, Gurevich Mikhail, Snider Justin, Hannun Yusuf A, Obeid Lina M
Health Science Center, L-4, 179, Stony Brook University Medical Center, Stony Brook, NY, 11794-8430, United States.
Health Science Center, L-4, 179, Stony Brook University Medical Center, Stony Brook, NY, 11794-8430, United States.
Prostaglandins Other Lipid Mediat. 2019 Apr;141:40-48. doi: 10.1016/j.prostaglandins.2019.02.005. Epub 2019 Feb 19.
Accumulation of deoxysphingolipids (deoxySLs) has been implicated in many neural diseases, although mechanisms remain unclear. A major obstacle limiting understanding of deoxySLs has been the lack of a method easily defining measurement of deoxydihydroceramide (deoxydhCer) and deoxyceramide (deoxyCer) in neural tissues. Furthermore, it is poorly understood if deoxySLs accumulate in the nervous system with aging. To facilitate investigation of deoxydhCer and deoxyCer in nervous system tissue, we developed a method to evaluate levels of these lipids in mouse brain, spinal cord, and sciatic nerve. Many deoxydhCers and brain C24-deoxyCer were present at 1, 3, and 6 months of age. Furthermore, while ceramide levels decreased with age, deoxydhCers increased in sciatic nerve and spinal cord, suggesting they may accumulate in peripheral nerves. C22-deoxydhCer was the highest deoxydhCer species in all tissues, suggesting it may be important physiologically. The development of this method will facilitate straightforward profiling of deoxydhCers and deoxyCers and the study of their metabolism and function. These results also reveal that deoxydhCers accumulate in peripheral nerves with normal aging.
脱氧鞘脂（deoxySLs）的积累与许多神经疾病有关，尽管其机制尚不清楚。限制对脱氧鞘脂理解的一个主要障碍是缺乏一种能够轻松测定神经组织中脱氧二氢神经酰胺（deoxydihydroceramide，deoxydhCer）和脱氧神经酰胺（deoxyceramide，deoxyCer）的方法。此外，对于脱氧鞘脂是否会随着衰老在神经系统中积累，人们了解甚少。为了便于研究神经系统组织中的脱氧二氢神经酰胺和脱氧神经酰胺，我们开发了一种方法来评估这些脂质在小鼠脑、脊髓和坐骨神经中的水平。在1个月、3个月和6个月大时，存在许多脱氧二氢神经酰胺和脑C24 - 脱氧神经酰胺。此外，虽然神经酰胺水平随年龄下降，但脱氧二氢神经酰胺在坐骨神经和脊髓中增加，表明它们可能在外周神经中积累。C22 - 脱氧二氢神经酰胺是所有组织中含量最高的脱氧二氢神经酰胺种类，表明它可能在生理上具有重要意义。这种方法的开发将有助于直接分析脱氧二氢神经酰胺和脱氧神经酰胺，并研究它们的代谢和功能。这些结果还表明，随着正常衰老，脱氧二氢神经酰胺在外周神经中积累。
