{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:09:02Z","timestamp":1787504942176,"version":"build-2736575974"},"reference-count":18,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council (BBSRC)","doi-asserted-by":"publisher","award":["BB\/M008770\/1"],"award-info":[{"award-number":["BB\/M008770\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The ability of sciatic nerve A fibres to conduct action potentials relies on an adequate supply of energy substrate, usually glucose, to maintain necessary ion gradients. Under our ex vivo experimental conditions, the absence of exogenously applied glucose triggers Schwann cell glycogen metabolism to lactate, which is transported to axons to fuel metabolism, with loss of the compound action potential (CAP) signalling glycogen exhaustion. The CAP failure is accelerated if tissue energy demand is increased by high-frequency stimulation (HFS) or by blocking lactate uptake into axons using cinnemate (CIN). Imposing HFS caused CAP failure in nerves perfused with 10 mM glucose, but increasing glucose to 30 mM fully supported the CAP and promoted glycogen storage. A combination of glucose and lactate supported the CAP more fully than either substrate alone, indicating the nerve is capable of simultaneously metabolising each substrate. CAP loss resulting from exposure to glucose-free artificial cerebrospinal fluid (aCSF) could be fully reversed in the absence of glycogen by addition of glucose or lactate when minimally stimulated, but imposing HFS resulted in only partial CAP recovery. The delayed onset of CAP recovery coincided with the release of lactate by Schwann cells, suggesting that functional Schwann cells are a prerequisite for CAP recovery.<\/jats:p>","DOI":"10.3390\/metabo12060505","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T03:33:18Z","timestamp":1654054398000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Energy Metabolism in Mouse Sciatic Nerve A Fibres during Increased Energy Demand"],"prefix":"10.3390","volume":"12","author":[{"given":"Laura R.","family":"Rich","sequence":"first","affiliation":[{"name":"School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce R.","family":"Ransom","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA"},{"name":"Department of Neuroscience, City University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-324X","authenticated-orcid":false,"given":"Angus M.","family":"Brown","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.cell.2011.02.018","article-title":"Astrocyte-neuron lactate transport is required for long-term memory formation","volume":"144","author":"Suzuki","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrn.2018.19","article-title":"Lactate in the brain: From metabolic end-product to signalling molecule","volume":"19","author":"Magistretti","year":"2018","journal-title":"Nat. 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