Deciphering the Lipid Architecture of the Rat Sciatic Nerve Using Imaging Mass Spectrometry

Knowledge on the normal structure and molecular composition of the peripheral nerves is essential to understand their pathophysiology and to select the regeneration strategies after injury. However, the precise lipid composition of the normal peripheral nerve is still poorly known. Here, we present the first study of distribution of individual lipids in the mature sciatic nerve of rats by imaging mass spectrometry. Both positive and negative ion modes were used to detect, identify and in situ map 166 molecular species of mainly glycerophospholipids, sphingomyelins, sulfatides, and diacyl and triacylglycerols. In parallel, lipid extracts were analyzed by LC-MS/MS to verify and complement the identification of lipids directly from the whole tissue. Three anatomical regions were clearly identified by its differential lipid composition: the nerve fibers, the connective tissue and the adipose tissue that surrounds the nerve. Unexpectedly, very little variety of phosphatidylcholine (PC) species was found, being by far PC 34:1 the most abundant species. Also, a rich composition on sulfatides was detected in fibers, probably due to the important role they play in the myelin cover around axons, as well as an abundance of storage lipids in the adipose and connective tissues. The database of lipids here presented for each region and for the whole sciatic nerve is a first step toward understanding the variety of the peripheral nerves' lipidome and its changes associated with different diseases and mechanical injuries.