Ganglioside lipidomics of CNS myelination using direct infusion shotgun mass spectrometry
Martina Arends,
Melanie Weber,
Cyrus Papan,
Markus Damm,
Michal A. Surma,
Christopher Spiegel,
Minou Djannatian,
Shengrong Li,
Lisa Connell,
Ludger Johannes,
Martina Schifferer,
Christian Klose,
Mikael Simons
Affiliations
Martina Arends
Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany
Melanie Weber
Lipotype, 01307 Dresden, Germany
Cyrus Papan
Lipotype, 01307 Dresden, Germany
Markus Damm
Lipotype, 01307 Dresden, Germany
Michal A. Surma
Lipotype, 01307 Dresden, Germany
Christopher Spiegel
Lipotype, 01307 Dresden, Germany
Minou Djannatian
Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany
Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany
Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany; Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, 81377 Munich, Germany; Corresponding author
Summary: Gangliosides are present and concentrated in axons and implicated in axon-myelin interactions, but how ganglioside composition changes during myelin formation is not known. Here, we present a direct infusion (shotgun) lipidomics method to analyze gangliosides in small amounts of tissue reproducibly and with high sensitivity. We resolve the mouse ganglioside lipidome during development and adulthood and determine the ganglioside content of mice lacking the St3gal5 and B4galnt1 genes that synthesize most ganglioside species. Our results reveal substantial changes in the ganglioside lipidome during the formation of myelinated nerve fibers. In sum, we provide insights into the CNS ganglioside lipidome with a quantitative and sensitive mass spectrometry method. Since this method is compatible with global lipidomic profiling, it will provide insights into ganglioside function in physiology and pathology.