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

doi:10.1016/j.isci.2022.105323

Ganglioside lipidomics of CNS myelination using direct infusion shotgun mass spectrometry

iScience. 2022 Oct 10;25(11):105323. doi: 10.1016/j.isci.2022.105323. eCollection 2022 Nov 18.

Authors

Martina Arends^{1

2}, Melanie Weber³, Cyrus Papan³, Markus Damm³, Michal A Surma³, Christopher Spiegel³, Minou Djannatian^{1

2}, Shengrong Li⁴, Lisa Connell⁴, Ludger Johannes⁵, Martina Schifferer^{1

2

6}, Christian Klose³, Mikael Simons^{1

2

6

7}

Affiliations

¹ Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany.
² German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany.
³ Lipotype, 01307 Dresden, Germany.
⁴ Avanti Lipids, 35007 Alabama, USA.
⁵ Institut Curie, Université PSL, U1143 INSERM, UMR3666 CNRS, 75248 Paris, France.
⁶ Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany.
⁷ Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, 81377 Munich, Germany.

Abstract

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.

Keywords: Cell biology; Neuroscience; Omics.