Quantifying 1-deoxydihydroceramides and 1-deoxyceramides in mouse nervous system tissue

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.