Abstract
Oligodendrocytes (OLs) generate lipid-rich myelin membranes that wrap axons to enable efficient transmission of electrical impulses. Using a RIT1 knockout mouse model and in situ high- resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) coupled with MS-based lipidomic analysis to determine the contribution of RIT1 to lipid homeostasis. Here, we report that RIT1 loss is associated with altered lipid levels in the central nervous system (CNS), including myelin-associated lipids within the corpus callosum (CC). Perturbed lipid metabolism was correlated with reduced numbers of OLs, but increased numbers of GFAP+ glia, in the CC, but not in grey matter. This was accompanied by reduced myelin protein expression and axonal conduction deficits. Behavioral analyses revealed significant changes in voluntary locomotor activity and anxiety-like behavior in RIT1KO mice. Together, these data reveal an unexpected role for RIT1 in the regulation of cerebral lipid metabolism, which coincide with altered white matter tract oligodendrocyte levels, reduced axonal conduction velocity, and behavioral abnormalities in the CNS.
Document Type
Article
Publication Date
10-2023
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.heliyon.2023.e20384
Funding Information
We would like to Mrs. Dana Napier for performing immunohistochemical-staining on tissue slices at the Markey Cancer Center. This work was supported by National Institutes of Health (NIH) grants R01 NS102196, R56NS124707 and Kentucky Spinal Cord and Head Injury Trust grant 16-1 awarded to Douglas A. Andres, NIH grant R01 MH125903 to Weikang Cai, NIH grant R01 AG033649 to Olivier Thibault, NIH grants R35 NS116824 and P01 NS097197 to Matthew S. Gentry, Hilaree N. Frazier was supported by NIH/NIA training grant T32AG057461, and Lyndsay E. A. Young was support by NIH/NCI F99CA2664165. This research was also supported by funding from the University of Kentucky Markey Cancer Center and the NIH-funded Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30 CA177558.
Repository Citation
Wu, Lei; Wang, Fang; Moncman, Carole L.; Pandey, Mritunjay; Clarke, Harrison A.; Frazier, Hilaree N.; Young, Lyndsay E. A.; Gentry, Matthew S.; Cai, Weikang; Thibault, Olivier; Sun, Ramon C.; and Andres, Douglas A., "RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities" (2023). Markey Cancer Center Faculty Publications. 388.
https://uknowledge.uky.edu/markey_facpub/388
Notes/Citation Information
2405-8440/© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).