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

Abstract

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.

Exploiting Sphingo- and Glycerophospholipid Impairment to Select Effective Drugs and Biomarkers for CMT1A

“…To map this aberrant lipid profile directly into the intact rat sciatic nerve, we performed MALDI-IMS [ Figure S3; (60)]: the clustering algorithm classified the two genotypes in clearly separate groups just in the endoneurium. Importantly, we also confirmed SP and GP as the most compromised pathways (Figures S4-S8).…”

The leptin receptor mutation of the obese Zucker rat causes sciatic nerve demyelination with a centripetal pattern defect

“…3,6,108,[121][122][123]126,127 However, many PNS nerve fibers owe large number of membrane wrappings; this more complex architecture leaves unresolved questions, compared with those now obtained with some CNS myelinated ones 3,5,102,106,109,111,116,[128][129][130][131][132][133][134] and others found with demyelination diseases especially linked with autoimmune or genetic defects. [1][2][3][4][5][6][7]124,125,[131][132][133][134][135][136][137][138][139][140][141][142][143][144] The choice of using sciatic nerve samples in the Zucker rats has been influenced by the frequent studies done on this nerve throughout the literature [1][2]…”

Common and Differential Traits of the Membrane Lipidome of Colon Cancer Cell Lines and Their Secreted Vesicles: Impact on Studies Using Cell Lines

“…Solid advances in the field of lipid analysis have facilitated access to detailed descriptions of many different lipidomes [4,7,9,10], while the irruption of imaging mass spectrometry techniques providing the bidimensional distribution of each lipid species across a tissue section has undoubtedly demonstrated how specific this distribution is [8,[11][12][13][14]. Lipidomic results often yield complex scenarios, with hundreds of different lipids changing in a highly ordered and orchestrated manner by mechanisms yet to be defined.…”