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In previous studies, we found a deficiency of <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> associated with the developmental deficit in congenital and neonatal HC. In this study, we therefore aimed to investigate the role of <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content> in folate transport and metabolism during the brain development of the congenital hydrocephalic Texas (H\u2010Tx) rat and normal (Sprague\u2013Dawley) rats. We show that at embryonic (E) stage E18 and E20, <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content>\u2010positive cells and\/or vesicles derived from the cortex can bind methyl\u2010folate similarly to folate receptor alpha, the main folate transporter. Hydrocephalic rats expressed diminished nuclear <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content> in both liver and brain at all postnatal (P) ages tested (P5, P15, and P20) together with a parallel increase in hepatic nuclear methyl\u2010folate at P5 and cerebral methylfolate at P15 and P20. A similar relationship was found between <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content> and 5\u2010methyl cytosine, the main marker for <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation. The data indicated that <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content> binds and transports methylfolate in the brain and that decreased liver and brain nuclear expression of <jats:styled-content style=\"fixed-case\">FDH<\/jats:styled-content> is linked with decreased <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation which could be a key factor in the developmental deficits associated with congenital and neonatal HC.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13686-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nFolate deficiency is associated with neurodevelopmental disorders such as neural tube defects and hydrocephalus. 10\u2010formyl\u2010tetrahydrofolate\u2010dehydrogenase (FDH) is a key regulator for folate availability and metabolic interconversion. We show that FDH binds and transports methylfolate in the brain. Moreover, we found that a deficiency of FDH in the nucleus of brain and liver is linked with decreased DNA methylation which could be a key factor in the developmental deficits associated with congenital and neonatal hydrocephalus cells.\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13686","type":"journal-article","created":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T12:37:50Z","timestamp":1465821470000},"page":"610-623","source":"Crossref","is-referenced-by-count":18,"title":["Neonatal hydrocephalus is a result of a block in\u00a0folate handling and metabolism involving 10\u2010formyltetrahydrofolate dehydrogenase"],"prefix":"10.1111","volume":"138","author":[{"given":"Naila","family":"Naz","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences The University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia Requena","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences The University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sanjuan\u2010Vilaplana","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences The University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Gurney","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences The University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaleel","family":"Miyan","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences The University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2007.10.010"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00980"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4833"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn262"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20632"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-6-S1-S25"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11338"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.111.000992"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.020"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20286"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm028"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5372.2107"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(94)90061-2"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2008.03185.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws122"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3123"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0885-8"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.12.001"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-6-10"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67052030.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181b44a5a"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6934"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1988.tb00887.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(90)90250-X"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59259-725-3_2"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687744"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.09.007"},{"key":"e_1_2_7_29_1","first-page":"227","article-title":"10\u2010formyltetrahydrofolate dehydrogenase, one of the major folate enzymes, is down\u2010regulated in tumor tissues and possesses suppressor effects on cancer cells","volume":"13","author":"Krupenko S. 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