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The involvement of branched chain amino acids (BCAAs) in this is largely unexplored. Transport of BCAAs at the plasma membrane is facilitated by SLC7A5\/SLC3A2, which increase with hypoxia. We hypothesized that hypoxia would alter BCAA transport and metabolism in the neonatal brain. We investigated this using an organotypic forebrain slice culture model with, the SLC7A5\/SLC3A2 inhibitor, 2-Amino-2-norbornanecarboxylic acid (BCH) under normoxic or hypoxic conditions. We subsequently analysed the metabolome and candidate gene expression. Hypoxia was associated with increased expression of<jats:italic>SLC7A5<\/jats:italic>and<jats:italic>SLC3A2<\/jats:italic>and an increased tissue abundance of BCAAs. Incubation of slices with<jats:sup>13<\/jats:sup>C-leucine confirmed that this was due to increased cellular uptake. BCH had little effect on metabolite abundance under normoxic or hypoxic conditions. This suggests hypoxia drives increased cellular uptake of BCAAs in the neonatal mouse forebrain, and membrane mediated transport through<jats:italic>SLC7A5<\/jats:italic>and<jats:italic>SLC3A2<\/jats:italic>is not essential for this process. This indicates mechanisms exist to generate the compounds required to maintain essential metabolism in the absence of external nutrient supply. Moreover, excess BCAAs have been associated with developmental delay, providing an unexplored mechanism of hypoxia mediated pathogenesis in the developing forebrain.<\/jats:p>","DOI":"10.1038\/s41598-021-88757-9","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T10:13:30Z","timestamp":1619518410000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Metabolic adaptations to hypoxia in the neonatal mouse forebrain can occur independently of the transporters SLC7A5 and SLC3A2"],"prefix":"10.1038","volume":"11","author":[{"given":"Eamon","family":"Fitzgerald","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennie","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Tennant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Boardman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda J.","family":"Drake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"88757_CR1","doi-asserted-by":"publisher","first-page":"F301","DOI":"10.1136\/archdischild-2017-313707","volume":"103","author":"C Gale","year":"2018","unstructured":"Gale, C. et al. 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