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R. Soc. B."],"published-print":{"date-parts":[[2022,7,27]]},"abstract":"<jats:p>Neural activity is costly and requires continuous ATP from aerobic metabolism. Brainstem motor function of American bullfrogs normally collapses after minutes of ischaemia, but following hibernation, it becomes ischaemia-tolerant, generating output for up to 2 h without oxygen or glucose delivery. Transforming the brainstem to function during ischaemia involves a switch to anaerobic glycolysis and brain glycogen. We hypothesized that improving neural performance during ischaemia involves a transcriptional program for glycogen and glucose metabolism. Here we measured mRNA copy number of genes along the path from glycogen metabolism to lactate production using real-time quantitative PCR. The expression of individual genes did not reflect enhanced glucose metabolism. However, the number of co-expressed gene pairs increased early into hibernation, and by the end, most genes involved in glycogen metabolism, glucose transport and glycolysis exhibited striking linear co-expression. By contrast, co-expression of genes in the Krebs cycle and electron transport chain decreased throughout hibernation. Our results uncover reorganization of the metabolic transcriptional network associated with a shift to ischaemia tolerance in brain function. We conclude that modifying gene co-expression may be a critical step in synchronizing storage and use of glucose to achieve ischaemia tolerance in active neural circuits.<\/jats:p>","DOI":"10.1098\/rspb.2022.1131","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T07:06:36Z","timestamp":1658905596000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Transformation to ischaemia tolerance of frog brain function corresponds to dynamic changes in mRNA co-expression across metabolic pathways"],"prefix":"10.1098","volume":"289","author":[{"given":"Min","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Biology, University of North Carolina at Greensboro, Greensboro, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-623X","authenticated-orcid":true,"given":"Joseph M.","family":"Santin","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Greensboro, Greensboro, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.019"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00062.2017"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2012.01.008"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.085381"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.00647"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.11.003"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00209.2020"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1968.tb08956.x"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0026-12.2012"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.042"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24241"},{"key":"e_1_3_7_13_2","first-page":"R49","article-title":"Anoxia-tolerant hepatocytes: model system for study of reversible metabolic suppression","volume":"265","author":"Buck LT","year":"1993","unstructured":"Buck LT, Land SC, Hochachka PW. 1993 Anoxia-tolerant hepatocytes: model system for study of reversible metabolic suppression. 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