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Neurons require substantial energy to execute action potentials, while the energy needs of oligodendrocytes are directed toward building the lipid\u2010rich components of myelin and supporting neuronal metabolism by transferring glycolytic products to axons as additional fuel. The utilization of energy metabolites in the brain parenchyma is tightly regulated to meet the needs of different cell types. Disruption of the supply of metabolites can lead to stress and oligodendrocyte injury, contributing to various neurological disorders, including some demyelinating diseases. Understanding the physiological properties, structures, and mechanisms involved in oligodendrocyte energy metabolism, as well as the relationship between oligodendrocytes and neighboring cells, is crucial to investigate the underlying pathophysiology caused by metabolic impairment in these disorders. In this review, we describe the particular physiological properties of oligodendrocyte energy metabolism and the response of oligodendrocytes to metabolic stress. We delineate the relationship between oligodendrocytes and other cells in the context of the neurovascular unit, and the regulation of metabolite supply according to energetic needs. We focus on the specific bioenergetic requirements of oligodendrocytes and address the disruption of metabolic energy in demyelinating diseases. We encourage further studies to increase understanding of the significance of metabolic stress on oligodendrocyte injury, to support the development of novel therapeutic approaches for the treatment of demyelinating diseases.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16219-fig-0006-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16219","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T05:49:28Z","timestamp":1725947368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["From\n                    <scp>BBB<\/scp>\n                    to\n                    <scp>PPP<\/scp>\n                    : Bioenergetic requirements and challenges for oligodendrocytes in health and disease"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1536-5083","authenticated-orcid":false,"given":"Milton Guilherme Forestieri","family":"Fernandes","sequence":"first","affiliation":[{"name":"Neuroimmunological Diseases and Glia Biology Research Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-3673","authenticated-orcid":false,"given":"Florian","family":"Pernin","sequence":"additional","affiliation":[{"name":"Neuroimmunological Diseases and Glia Biology Research Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5148-0636","authenticated-orcid":false,"given":"Jack P.","family":"Antel","sequence":"additional","affiliation":[{"name":"Neuroimmunological Diseases and Glia Biology Research Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-5080","authenticated-orcid":false,"given":"Timothy E.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Neuroimmunological Diseases and Glia Biology Research Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011625"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.1.25"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.08.008"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2589-x"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23250"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-021-00814-4"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"e_1_2_13_10_1","doi-asserted-by":"crossref","unstructured":"Asadollahi E. 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