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An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation
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 control...
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/PMC10568429/ https://www.ncbi.nlm.nih.gov/pubmed/37841597 http://dx.doi.org/10.1016/j.isci.2023.107921 |
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author | 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 |
author_facet | 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 |
author_sort | Suhail, Hamid |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10568429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105684292023-10-13 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 iScience Article 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. Elsevier 2023-09-15 /pmc/articles/PMC10568429/ /pubmed/37841597 http://dx.doi.org/10.1016/j.isci.2023.107921 Text en © 2023 The Author(s) 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 | Article 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 An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
title | An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
title_full | An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
title_fullStr | An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
title_full_unstemmed | An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
title_short | An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
title_sort | early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568429/ https://www.ncbi.nlm.nih.gov/pubmed/37841597 http://dx.doi.org/10.1016/j.isci.2023.107921 |
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