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RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities()
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 l...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539968/ https://www.ncbi.nlm.nih.gov/pubmed/37780758 http://dx.doi.org/10.1016/j.heliyon.2023.e20384 |
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author | 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. Andres, Douglas A. |
author_facet | 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. Andres, Douglas A. |
author_sort | Wu, Lei |
collection | PubMed |
description | 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 RIT1(KO) 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. |
format | Online Article Text |
id | pubmed-10539968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105399682023-09-30 RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() 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. Andres, Douglas A. Heliyon Research Article 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 RIT1(KO) 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. Elsevier 2023-09-23 /pmc/articles/PMC10539968/ /pubmed/37780758 http://dx.doi.org/10.1016/j.heliyon.2023.e20384 Text en © 2023 The Authors. Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article 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. Andres, Douglas A. RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
title | RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
title_full | RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
title_fullStr | RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
title_full_unstemmed | RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
title_short | RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
title_sort | rit1 regulation of cns lipids rit1 deficiency alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities() |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539968/ https://www.ncbi.nlm.nih.gov/pubmed/37780758 http://dx.doi.org/10.1016/j.heliyon.2023.e20384 |
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