{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:45:38Z","timestamp":1782924338878,"version":"3.54.5"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Behavioural Brain Research"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.bbr.2025.115941","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T02:41:27Z","timestamp":1763606487000},"page":"115941","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Increased dietary levels of folic acid reduce survival and alters climbing behaviors 24\u202fh after hypoxia in male and female Drosophila melanogaster"],"prefix":"10.1016","volume":"499","author":[{"given":"Siddarth","family":"Gunnala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Juba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Ashcraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meher","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori M.","family":"Buhlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-7307","authenticated-orcid":false,"given":"Nafisa M.","family":"Jadavji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbr.2025.115941_bib1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.reprotox.2018.05.004","article-title":"Folic acid and primary prevention of neural tube defects: a review","volume":"80","author":"Van Gool","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.bbr.2025.115941_bib2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/1028415X.2016.1236174","article-title":"Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury","volume":"21","author":"Lucke-Wold","year":"2018","journal-title":"Nutr. Neurosci."},{"key":"10.1016\/j.bbr.2025.115941_bib3","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/nutrit\/nuw015","article-title":"Safe use of high intakes of folic acid: research challenges and paths forward","volume":"74","author":"Boyles","year":"2016","journal-title":"Nutr. Rev."},{"key":"10.1016\/j.bbr.2025.115941_bib4","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1515\/cclm-2012-0561","article-title":"Molecular mechanisms underlying the potentially adverse effects of folate","volume":"51","author":"Strickland","year":"2013","journal-title":"Clin. Chem. Lab Med."},{"key":"10.1016\/j.bbr.2025.115941_bib5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1158\/1055-9965.EPI-06-0054","article-title":"Folate supplementation: too much of a good thing?","volume":"15","author":"Ulrich","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"10.1016\/j.bbr.2025.115941_bib6","first-page":"84","article-title":"Folate: is too much of a good thing harmful?","volume":"26","author":"Mullin","year":"2011","journal-title":"Nutr. Clin. Pract. Off. Publ. Am. Soc. Parenter. Enter. Nutr."},{"key":"10.1016\/j.bbr.2025.115941_bib7","first-page":"888","article-title":"High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring","author":"Bahous","year":"2017","journal-title":"Hum. Mol. Genet. 26"},{"key":"10.1016\/j.bbr.2025.115941_bib8","unstructured":"CDC, Folic Acid: Sources and Recommended Intake, Folic Acid (2025). \u3008https:\/\/www.cdc.gov\/folic-acid\/about\/intake-and-sources.html\u3009 (accessed June 30, 2025)."},{"key":"10.1016\/j.bbr.2025.115941_bib9","series-title":"Folic Acid","article-title":"Folic Acid","author":"Merrell","year":"2024"},{"key":"10.1016\/j.bbr.2025.115941_bib10","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3945\/jn.114.201210","article-title":"Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults","volume":"145","author":"Pfeiffer","year":"2015","journal-title":"J. Nutr."},{"key":"10.1016\/j.bbr.2025.115941_bib11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1136\/svn-2018-000156","article-title":"B vitamins for stroke prevention","volume":"3","author":"Hankey","year":"2018","journal-title":"Stroke Vasc. Neurol."},{"key":"10.1016\/j.bbr.2025.115941_bib12","doi-asserted-by":"crossref","DOI":"10.1001\/jama.2015.2274","article-title":"Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial","volume":"313","author":"Huo","year":"2015","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"10.1016\/j.bbr.2025.115941_bib13","article-title":"Folic acid represses hypoxia-induced inflammation in THP-1 cells through inhibition of the PI3K\/Akt\/HIF-1\u03b1 pathway","volume":"11","author":"Huang","year":"2016","journal-title":"Plos One"},{"key":"10.1016\/j.bbr.2025.115941_bib14","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.nutres.2018.03.007","article-title":"Folic acid supplementation repressed hypoxia-induced inflammatory response via ROS and JAK2\/STAT3 pathway in human promyelomonocytic cells","volume":"53","author":"Ma","year":"2018","journal-title":"Nutr. Res."},{"key":"10.1016\/j.bbr.2025.115941_bib15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s12013-016-0723-z","article-title":"Folic acid attenuates vascular endothelial cell injury caused by hypoxia via the inhibition of ERK1\/2\/NOX4\/ROS pathway","volume":"74","author":"Cheng","year":"2016","journal-title":"Cell Biochem. Biophys."},{"key":"10.1016\/j.bbr.2025.115941_bib16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3233\/JAD-160329","article-title":"Multi-vitamin B supplementation reverses hypoxia-induced tau hyperphosphorylation and improves memory function in adult mice","volume":"54","author":"Yu","year":"2016","journal-title":"J. Alzheimer\u2019S. Dis."},{"key":"10.1016\/j.bbr.2025.115941_bib17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-1-59745-365-3_3","article-title":"Drosophila melanogaster as a model system to study mitochondrial biology","volume":"372","author":"Fern\u00e1ndez-Moreno","year":"2007","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.bbr.2025.115941_bib18","series-title":"Stroke Reperfusion Injury","article-title":"Stroke Reperfusion Injury","author":"Mandalaneni","year":"2025"},{"key":"10.1016\/j.bbr.2025.115941_bib19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0092-8674(00)80610-8","article-title":"Nitric oxide contributes to behavioral, cellular, and developmental responses to low oxygen in Drosophila","volume":"98","author":"Wingrove","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.bbr.2025.115941_bib20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/fly.5.2.14284","article-title":"Behavioral responses to hypoxia and hyperoxia in Drosophila larvae: molecular and neuronal sensors","volume":"5","author":"Morton","year":"2011","journal-title":"Fly"},{"key":"10.1016\/j.bbr.2025.115941_bib21","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jchromb.2018.06.008","article-title":"Simultaneous measurement of folate cycle intermediates in different biological matrices using liquid chromatography\u2013tandem mass spectrometry","volume":"1092","author":"Nandania","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"10.1016\/j.bbr.2025.115941_bib22","first-page":"52741","article-title":"Quantitative analysis of climbing defects in a Drosophila model of neurodegenerative disorders","author":"Madabattula","year":"2015","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.bbr.2025.115941_bib23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.vascn.2014.08.006","article-title":"Computational tools for fitting the hill equation to dose-response curves","volume":"71","author":"Gadagkar","year":"2015","journal-title":"J. Pharm. Toxicol. Methods"},{"key":"10.1016\/j.bbr.2025.115941_bib24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0006-8993(98)00286-8","article-title":"Hypoxia-induced apoptosis: effect of hypoxic severity and role of p53 in neuronal cell death","volume":"797","author":"Banasiak","year":"1998","journal-title":"Brain Res."},{"key":"10.1016\/j.bbr.2025.115941_bib25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.nbd.2017.04.001","article-title":"B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke","volume":"103","author":"Jadavji","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.bbr.2025.115941_bib26","article-title":"W. Re, What can the common fruit fly teach us about stroke?: lessons learned from the hypoxic tolerant Drosophila melanogaster","volume":"18","author":"Ps","year":"2024","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.bbr.2025.115941_bib27","doi-asserted-by":"crossref","DOI":"10.3390\/brainsci7110149","article-title":"Is high folic acid intake a risk factor for autism?\u2014a review","volume":"7","author":"Wiens","year":"2017","journal-title":"Brain Sci."},{"key":"10.1016\/j.bbr.2025.115941_bib28","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/nutrit\/nuy025","article-title":"Maternal oversupplementation with folic acid and its impact on neurodevelopment of offspring","volume":"76","author":"Murray","year":"2018","journal-title":"Nutr. Rev."},{"key":"10.1016\/j.bbr.2025.115941_bib29","article-title":"Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts","volume":"39","author":"Moore","year":"2014","journal-title":"J. Alzheimer\u2019S. Dis."},{"key":"10.1016\/j.bbr.2025.115941_bib30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0084635","article-title":"Folic Acid supplementation promotes mammary tumor progression in a rat model","volume":"9","author":"Deghan Manshadi","year":"2014","journal-title":"PloS One"},{"key":"10.1016\/j.bbr.2025.115941_bib31","first-page":"1","article-title":"Dietary folic acid deficiency impacts hippocampal morphology and cortical acetylcholine metabolism in adult male and female mice","author":"Bennett","year":"2021","journal-title":"Nutr. Neurosci."},{"key":"10.1016\/j.bbr.2025.115941_bib32","doi-asserted-by":"crossref","first-page":"393","DOI":"10.5483\/BMBRep.2021.54.8.052","article-title":"Proprioception, the regulator of motor function","volume":"54","author":"Moon","year":"2021","journal-title":"BMB Rep."},{"key":"10.1016\/j.bbr.2025.115941_bib33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.conb.2019.01.013","article-title":"The development and assembly of the Drosophila adult ventral nerve cord","volume":"56","author":"Venkatasubramanian","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"10.1016\/j.bbr.2025.115941_bib34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-genom-091212-153439","article-title":"Genetic analysis of hypoxia tolerance and susceptibility in Drosophila and humans","volume":"14","author":"Zhou","year":"2013","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"10.1016\/j.bbr.2025.115941_bib35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0022-1910(96)00084-4","article-title":"Behavioral and electrophysiologic responses of Drosophila melanogaster to prolonged periods of Anoxia","volume":"43","author":"Haddad","year":"1997","journal-title":"J. Insect Physiol."},{"key":"10.1016\/j.bbr.2025.115941_bib36","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0005371","article-title":"Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster","volume":"4","author":"Azad","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.bbr.2025.115941_bib37","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1242\/jeb.031179","article-title":"Metabolic function in Drosophila melanogaster in response to hypoxia and pure oxygen","volume":"212","author":"Van Voorhies","year":"2009","journal-title":"J. Exp. Biol."},{"key":"10.1016\/j.bbr.2025.115941_bib38","doi-asserted-by":"crossref","DOI":"10.1186\/s12918-018-0621-7","article-title":"Sex differences in hepatic one-carbon metabolism","volume":"12","author":"Sadre-Marandi","year":"2018","journal-title":"BMC Syst. Biol."},{"key":"10.1016\/j.bbr.2025.115941_bib39","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.3390\/nu14235077","article-title":"Diet supplementation with polyphenol-rich salicornia ramosissima extracts protects against tissue damage in experimental models of cerebral ischemia","volume":"14","author":"Garc\u00eda-Rodr\u00edguez","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.bbr.2025.115941_bib40","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s12276-021-00565-3","article-title":"Posthypoxic behavioral impairment and mortality of Drosophila melanogaster are associated with high temperatures, enhanced predeath activity and oxidative stress","volume":"53","author":"Habib","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.bbr.2025.115941_bib41","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/cdd.2016.158","article-title":"dATF4 regulation of mitochondrial folate-mediated one-carbon metabolism is neuroprotective","volume":"24","author":"Celardo","year":"2017","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.bbr.2025.115941_bib42","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev.genet.37.040103.095211","article-title":"Genetics of aging in the fruit fly, drosophila melanogaster","volume":"37","author":"Helfand","year":"2003","journal-title":"Annu. Rev. Genet."},{"key":"10.1016\/j.bbr.2025.115941_bib43","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1186\/s12889-024-19134-0","article-title":"An international perspective on young stroke incidence and risk factors: a scoping review","volume":"24","author":"Amoah","year":"2024","journal-title":"BMC Public Health"},{"key":"10.1016\/j.bbr.2025.115941_bib44","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.3390\/nu15183891","article-title":"The role of one-carbon metabolism in healthy brain aging","volume":"15","author":"Virdi","year":"2023","journal-title":"Nutrients"},{"key":"10.1016\/j.bbr.2025.115941_bib45","doi-asserted-by":"crossref","first-page":"841","DOI":"10.2174\/1871527322666230215144649","article-title":"Electrolyte imbalance and neurologic injury","volume":"23","author":"Poe","year":"2024","journal-title":"CNS Neurol. Disord. Drug Targets"}],"container-title":["Behavioural Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166432825005285?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166432825005285?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:29:14Z","timestamp":1765204154000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166432825005285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":45,"alternative-id":["S0166432825005285"],"URL":"https:\/\/doi.org\/10.1016\/j.bbr.2025.115941","relation":{},"ISSN":["0166-4328"],"issn-type":[{"value":"0166-4328","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Increased dietary levels of folic acid reduce survival and alters climbing behaviors 24\u202fh after hypoxia in male and female Drosophila melanogaster","name":"articletitle","label":"Article Title"},{"value":"Behavioural Brain Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbr.2025.115941","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115941"}}