{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:46:17Z","timestamp":1773665177458,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T00:00:00Z","timestamp":1398729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin C (VitC) has several roles in the brain acting both as a specific and  non-specific antioxidant. The brain upholds a very high VitC concentration and is able to preferentially retain VitC even during deficiency. The accumulation of brain VitC levels much higher than in blood is primarily achieved by the sodium dependent VitC transporter (SVCT2). This study investigated the effects of chronic pre-and postnatal VitC deficiency as well as the effects of postnatal VitC repletion, on brain SVCT2 expression and markers of oxidative stress in young guinea pigs. Biochemical analyses demonstrated significantly decreased total VitC and an increased percentage of dehydroascorbic acid, as well as increased lipid oxidation (malondialdehyde), in the brains of VitC deficient animals  (p &lt; 0.0001) compared to controls. VitC repleted animals were not significantly different from controls. No significant changes were detected in either gene or protein expression of SVCT2 between groups or brain regions. In conclusion, chronic pre-and postnatal VitC deficiency increased brain redox imbalance but did not increase SVCT2 expression. Our findings show potential implications for VitC deficiency induced negative effects of redox imbalance in the brain and provide novel insight to the regulation of VitC in the brain during deficiency.<\/jats:p>","DOI":"10.3390\/nu6051809","type":"journal-article","created":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T04:40:45Z","timestamp":1398832845000},"page":"1809-1822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Chronic Vitamin C Deficiency Promotes Redox Imbalance in the Brain but Does Not Alter Sodium-Dependent Vitamin C Transporter 2 Expression"],"prefix":"10.3390","volume":"6","author":[{"given":"Maya","family":"Paidi","sequence":"first","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C 1870, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janne","family":"Schjoldager","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C 1870, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-8407","authenticated-orcid":false,"given":"Jens","family":"Lykkesfeldt","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C 1870, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille","family":"Tveden-Nyborg","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C 1870, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1203\/00006450-200205000-00005","article-title":"Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children","volume":"51","author":"Bayir","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.braindev.2008.06.010","article-title":"Ascorbic acid protects the newborn rat brain from hypoxic-ischemia","volume":"31","author":"Miura","year":"2009","journal-title":"Brain Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0166-2236(99)01543-X","article-title":"Ascorbate regulation and its neuroprotective role in the brain","volume":"23","author":"Rice","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/0301-0082(94)90052-3","article-title":"A vitamin as neuromodulator: Ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission","volume":"43","author":"Rebec","year":"1994","journal-title":"Prog. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1079\/BJN19710048","article-title":"The retention of ascorbic acid by guinea-pig tissues","volume":"26","author":"Hughes","year":"1971","journal-title":"Br. J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/S0306-4522(97)00347-3","article-title":"Differential compartmentalization of brain ascorbate and glutathione between neurons and glia","volume":"82","author":"Rice","year":"1997","journal-title":"Neuroscience"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S1532-0456(03)00167-4","article-title":"Oxidative stress in liver and brain of the hatchling chicken (Gallus domesticus) following in ovo injection with TCDD","volume":"136","author":"Hilscherova","year":"2003","journal-title":"Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S1532-0456(02)00116-3","article-title":"Brain antioxidant regulation in mammals and anoxia-tolerant reptiles: Balanced for neuroprotection and neuromodulation","volume":"133","author":"Rice","year":"2002","journal-title":"Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.jnutbio.2003.07.003","article-title":"Protective effect of vitamin C against the ethanol mediated toxic effects on human brain glial cells","volume":"14","author":"Paniagua","year":"2003","journal-title":"J. Nutr. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.brainres.2007.09.044","article-title":"Protective effects of ascorbic acid against lead-induced apoptotic neurodegeneration in the developing rat hippocampus in vivo","volume":"1185","author":"Hart","year":"2007","journal-title":"Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0197-4580(98)00009-8","article-title":"Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer\u2019s disease","volume":"19","author":"Markesbery","year":"1998","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.neulet.2005.12.017","article-title":"Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment","volume":"397","author":"Butterfield","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/ajcn\/54.4.712","article-title":"Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum","volume":"54","author":"Dhariwal","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.3390\/nu5082860","article-title":"Regulation of Vitamin C Homeostasis during Deficiency","volume":"5","author":"Lindblad","year":"2013","journal-title":"Nutrients"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.freeradbiomed.2008.12.018","article-title":"Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2","volume":"46","author":"Harrison","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/19986","article-title":"A family of mammalian Na+-dependent L-ascorbic acid transporters","volume":"399","author":"Tsukaguchi","year":"1999","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/0502-514","article-title":"Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival","volume":"8","author":"Sotiriou","year":"2002","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.freeradbiomed.2010.06.008","article-title":"Low vitamin C increased oxidative stress cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2","volume":"49","author":"Harrison","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/j.1742-7843.2011.00852.x","article-title":"Chronic Vitamin C Deficiency does not Accelerate Oxidative Stress in Ageing Brains of Guinea Pigs","volume":"110","author":"Hasselholt","year":"2012","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.brainres.2010.05.090","article-title":"Vitamin C distribution and retention in the mouse brain","volume":"1348","author":"Harrison","year":"2010","journal-title":"Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1016\/j.freeradbiomed.2012.02.017","article-title":"Essential role of intracellular glutathione in controlling ascorbic acid transporter expression and function in rat hepatocytes and hepatoma cells","volume":"52","author":"Mardones","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.bbrc.2011.09.146","article-title":"Differential regulation of the ascorbic acid transporter SVCT2 during development and in response to ascorbic acid depletion","volume":"414","author":"Meredith","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.abb.2010.01.012","article-title":"Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30\/GNL knockout mice","volume":"496","author":"Amano","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21967","DOI":"10.1016\/S0021-9258(19)36707-9","article-title":"Guinea pigs possess a highly mutated gene for l-gulono-gamma-lactone oxidase, the key enzyme for l-ascorbic acid biosynthesis missing in this species","volume":"267","author":"Nishikimi","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1017\/S0007114507787457","article-title":"Vitamin C deficiency in weanling guinea pigs: Differential expression of oxidative stress and DNA repair in liver and brain","volume":"98","author":"Lykkesfeldt","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3945\/ajcn.2009.27954","article-title":"Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs","volume":"90","author":"Johansen","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e48488","DOI":"10.1371\/journal.pone.0048488","article-title":"Maternal Vitamin C Deficiency during Pregnancy Persistently Impairs Hippocampal Neurogenesis in Offspring of Guinea Pigs","volume":"7","author":"Vogt","year":"2012","journal-title":"PLoS One"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1006\/abio.2000.4592","article-title":"Determination of Ascorbic Acid and Dehydroascorbic Acid in Biological Samples by High-Performance Liquid Chromatography Using Subtraction Methods: Reliable Reduction with Tris[2-carboxyethyl] phosphine Hydrochloride","volume":"282","author":"Lykkesfeldt","year":"2000","journal-title":"Anals Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/clinchem\/47.9.1725","article-title":"Determination of malondialdehyde as dithiobarbituric acid adduct in biological samples by HPLC with fluorescence detection: Comparison with ultraviolet-visible spectrophotometry","volume":"47","author":"Lykkesfeldt","year":"2001","journal-title":"Clin. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/0003-2697(76)90326-2","article-title":"A fluorometric method for determination of oxidized and reduced glutathione in tissues","volume":"74","author":"Hissin","year":"1976","journal-title":"An. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0945-053X(01)00193-7","article-title":"The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants","volume":"21","author":"Clark","year":"2002","journal-title":"Matrix Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.bbrc.2007.06.072","article-title":"Maturational loss of the vitamin C transporter in erythrocytes","volume":"360","author":"May","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.bbrc.2007.07.007","article-title":"Redox regulation of vitamin C transporter SVCT2 in C2C12 myotubes","volume":"361","author":"Savini","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1017\/S0007114513000913","article-title":"Prolonged maternal vitamin C deficiency overrides preferential fetal ascorbate transport but does not influence perinatal survival in guinea pigs","volume":"110","author":"Schjoldager","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.brainres.2010.06.037","article-title":"Low ascorbic acid and increased oxidative stress in Gulo\u2212\/\u2212 mice during development","volume":"1349","author":"Harrison","year":"2010","journal-title":"Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/ajcn\/58.1.103","article-title":"Vitamin C elevates red blood cell glutathione in healthy adults","volume":"58","author":"Johnston","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/1071576022411256","article-title":"Increased oxidative damage in vitamin C deficiency is accompanied by induction of ascorbic acid recycling capacity in young but not mature guinea pigs","volume":"36","author":"Lykkesfeldt","year":"2002","journal-title":"Free Radic. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1046\/j.1471-4159.2001.00461.x","article-title":"High-affinity sodium\u2013vitamin C co-transporters (SVCT) expression in embryonic mouse neurons","volume":"78","author":"Castro","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/glia.20133","article-title":"Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells","volume":"50","author":"Salazar","year":"2005","journal-title":"Glia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/jnr.20751","article-title":"Immunohistochemical study of the distribution of sodium-dependent vitamin C transporters in adult rat brain","volume":"83","author":"Mun","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-94-007-2199-9_6","article-title":"Vitamin C Transport and Its Role in the Central Nervous System","volume":"56","author":"Olaf","year":"2012","journal-title":"Water Soluble Vitamins"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.freeradbiomed.2006.11.028","article-title":"Translational control of the ascorbic acid transporter SVCT2 in human platelets","volume":"42","author":"Savini","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/j.1471-4159.2008.05788.x","article-title":"The Na+-dependent l-ascorbic acid transporter SVCT2 expressed in brainstem cells, neurons, and neuroblastoma cells is inhibited by flavonoids","volume":"108","author":"Caprile","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00418-012-1027-z","article-title":"Dynamic expression of the sodium-vitamin C co-transporters, SVCT1 and SVCT2, during perinatal kidney development","volume":"139","author":"Nualart","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/j.1471-4159.2008.05469.x","article-title":"Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid","volume":"106","author":"Harrison","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.redox.2014.01.009","article-title":"Prenatal vitamin C deficiency results in differential levels of oxidative stress during late gestation in foetal guinea pig brains","volume":"2","author":"Paidi","year":"2014","journal-title":"Redox Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1046\/j.1471-4159.2003.01891.x","article-title":"Effect of middle cerebral artery occlusion on mRNA expression for the sodium-coupled vitamin C transporter SVCT2 in rat brain","volume":"86","author":"Berger","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e17139","DOI":"10.1371\/journal.pone.0017139","article-title":"Sodium-dependent vitamin C transporter 2 (SVCT2) expression and activity in brain capillary endothelial cells after transient ischemia in mice","volume":"6","author":"Gess","year":"2011","journal-title":"PLoS One"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.bbrc.2008.06.120","article-title":"N-Glycosylation is required for Na+-dependent vitamin C transporter functionality","volume":"374","author":"Subramanian","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.abb.2009.02.010","article-title":"Oxidized lipoprotein induces the macrophage ascorbate transporter (SVCT2): Protection by intracellular ascorbate against oxidant stress and apoptosis","volume":"485","author":"Chi","year":"2009","journal-title":"Arch. Biochem. Biophys."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/6\/5\/1809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:10:51Z","timestamp":1760217051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/6\/5\/1809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,29]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5]]}},"alternative-id":["nu6051809"],"URL":"https:\/\/doi.org\/10.3390\/nu6051809","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,29]]}}}