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An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation.
Suhail, Hamid; Nematullah, Mohammad; Rashid, Faraz; Sajad, Mir; Fatma, Mena; Singh, Jaspreet; Zahoor, Insha; Cheung, Wing Lee; Tiwari, Nivedita; Ayasolla, Kameshwar; Kumar, Ashok; Hoda, Nasrul; Rattan, Ramandeep; Giri, Shailendra.
Afiliación
  • Suhail H; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Nematullah M; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Rashid F; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Sajad M; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Fatma M; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Singh J; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Zahoor I; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Cheung WL; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Tiwari N; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Ayasolla K; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Kumar A; Department of Ophthalmology/Kresge Eye Institute, Department of Anatomy and Cell Biology, Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA.
  • Hoda N; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Rattan R; Division of Gynecology Oncology, Department of Women's Health Services, Henry Ford Health System, Detroit, MI 48202, USA.
  • Giri S; Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
iScience ; 26(10): 107921, 2023 Oct 20.
Article en En | MEDLINE | ID: mdl-37841597
Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect oligodendrocyte activity during neuroinflammation is unknown. We demonstrate that activated microglial energy metabolism controls oligodendrocyte mitochondrial respiration and activity. Lipopolysaccharide/interferon gamma promote glycolysis and decrease mitochondrial respiration and myelin protein synthesis in rat brain glial cells. Enriched microglia showed an early burst in glycolysis. In microglia-conditioned medium, oligodendrocytes did not respire and expressed less myelin. SCENITH revealed metabolic derangement in microglia and O4-positive oligodendrocytes in endotoxemia and experimental autoimmune encephalitogenic models. The early burst of glycolysis in microglia was mediated by PDPK1 and protein kinase B/AKT signaling. We found that microglia-produced NO and itaconate, a tricarboxylic acid bifurcated metabolite, reduced mitochondrial respiration in oligodendrocytes. During inflammation, we discovered a signaling pathway in microglia that could be used as a therapeutic target to restore mitochondrial function in oligodendrocytes and induce remyelination.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos