{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T10:19:52Z","timestamp":1775384392829,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T00:00:00Z","timestamp":1354579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD067244"],"award-info":[{"award-number":["HD067244"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD072251"],"award-info":[{"award-number":["HD072251"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:p>\n                    Folate deficiency has been associated with many adverse clinical manifestations. The blood\u2010brain barrier (BBB), formed by brain capillary endothelial cells, protects the brain from exposure to neurotoxicants. The function of BBB is modulated by multiple ABC transporters, particularly P\u2010glycoprotein. A proton\u2010coupled folate transporter (PCFT)\u2010deficient mouse has been previously described as a model for systemic folate deficiency. Herein, we demonstrate that exposing mouse brain capillaries to the antiepileptic drug, valproic acid (VPA; 5 \u03bcM), significantly increased P\u2010glycoprotein transport function in the wild\u2010type animals. A ligand to the aryl hydrocarbon receptor, 2,3,7,8\u2010tetrachlorodibenzo\u2010\n                    <jats:italic>p<\/jats:italic>\n                    \u2010dioxin (TCDD), produced a similar induction of P\u2010glycoprotein, which tightened the BBB, thereby increasing the neuroprotection. However, VPA\u2010 or TCDD\u2010induced P\u2010glycoprotein transport was blocked in the PCFT\u2010nullizygous mice, indicating that multiple neuroprotective mechanisms are compromised under folate\u2010deficient conditions. Brain capillaries from\n                    <jats:italic>S<\/jats:italic>\n                    \u2010folinic acid (SFA; 40 mg\/kg)\u2010treated PCFT\u2010nullizygous mice exhibited increased P\u2010glycoprotein transport following VPA exposure. This suggests that SFA supplementation restored the normal BBB function. In addition, we show that tight\u2010junction proteins are disintegrated in the PCFT mutant mice. Taken together, these findings strongly suggest that folate deficiency disrupts the BBB function by targeting the transporter and tight junctions, which may contribute to the development of neurological disorders.\u2014Wang, X., Cabrera, R. M., Li, Y., Miller, D. S., Finnell, R. H. Functional regulation of P\u2010glycoprotein at the blood\u2010brain barrier in proton\u2010coupled folate transporter (PCFT) mutant mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 1167\u20131175 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-218495","type":"journal-article","created":{"date-parts":[[2012,12,5]],"date-time":"2012-12-05T20:49:29Z","timestamp":1354740569000},"page":"1167-1175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Functional regulation of P\u2010glycoprotein at the blood\u2010brain barrier in proton\u2010coupled folate transporter (PCFT) mutant mice"],"prefix":"10.1096","volume":"27","author":[{"given":"Xueqian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences The University of Texas at Austin Austin Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences The University of Texas at Austin Austin Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Confocal Microscopy Core Dell Pediatric Research Institute The University of Texas at Austin Austin Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology and Pharmacology National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences The University of Texas at Austin Austin Texas USA"},{"name":"Department of Chemistry and Biochemistry The University of Texas at Austin Austin Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1986"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443610701814195"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-165084"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.06.004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-072610-145133"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9159-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(02)00624-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.211.95"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/13861"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279653"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood\u2010brain barrier","volume":"37","author":"Abbott N. J.","journal-title":"Neurobiol. Dis."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.03.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209186200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2006.09.001"},{"key":"e_1_2_7_16_1","first-page":"2532","article-title":"Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2","volume":"59","author":"Hooijberg J. H.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01615-5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.063685"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-169227"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0026-895X(24)05623-2","article-title":"Pregnane X receptor up\u2010regulation of P\u2010glycoprotein expression and transport function at the blood\u2010brain barrier","volume":"66","author":"Bauer B.","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.268.1.F46"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.001503"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(24)12708-3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.023796"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.01.071"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.014456"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.107.07109"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1728"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.032854"},{"key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/jcbfm.2011.44","article-title":"Activating PKC\u2010beta1 at the blood\u2010brain barrier reverses induction of P\u2010glycoprotein activity by dioxin and restores drug delivery to the CNS","volume":"31","author":"Wang X.","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.55782\/ane-2011-1861","article-title":"Tight junctions in neurological diseases","volume":"71","author":"Bednarczyk J.","year":"2011","journal-title":"Acta Neurobiol. Exp. (Wars.)"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000082726.08631.E7"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000309223.98616.e4"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.08.005"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9196-1"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807665200"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c679df"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206953"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401725200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2005"},{"key":"e_1_2_7_41_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0022-3565(24)39291-2","article-title":"Expression and localization of multidrug resistant protein mrp2 in rat small intestine","volume":"293","author":"Mottino A. D.","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2008.11.003"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.12-218495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.12-218495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.12-218495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:02:08Z","timestamp":1761699728000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.12-218495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,4]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1096\/fj.12-218495"],"URL":"https:\/\/doi.org\/10.1096\/fj.12-218495","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,4]]},"assertion":[{"value":"2012-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}