{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:06Z","timestamp":1787013906358,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,2,20]],"date-time":"2014-02-20T00:00:00Z","timestamp":1392854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Valproic acid (\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    ), a short\u2010chain fatty acid, is used clinically as an anticonvulsant and mood stabilizer. Valproic acid also inhibits histone deacetylase activity, which is associated with histone hyperacetylation and changes in gene expression. In this study, we examined the effects of\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    on the expression of selected neurotrophic and differentiation factors in C17.2 neural stem cells. Reverse transcription\u2010polymerase chain reaction analysis revealed a significant increase in conserved dopamine neurotrophic factor (\n                    <jats:styled-content style=\"fixed-case\">CDNF<\/jats:styled-content>\n                    ) and glial cell line\u2010derived neurotrophic factor m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    expression, after treatment with clinically relevant concentrations of\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    (0.5 or 1.0\u00a0mM) for 24\u00a0hr. Increases in the protein expression of\n                    <jats:styled-content style=\"fixed-case\">CDNF<\/jats:styled-content>\n                    and mesencephalic astrocyte\u2010derived neurotrophic factor were also observed, after similar treatment with\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    . In addition, significant increases in the m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    levels of the early dopaminergic neuron marker, nuclear receptor\u2010related protein 1(Nurr1), and the transcriptional regulator, early growth response protein 1 (Egr1), were observed after treatment with\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    for 24\u00a0hr. C17.2 neural stem cells exhibited high basal m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    expression of brain\u2010derived neurotrophic factor and SRY (sex determining region Y)\u2010box 2 (Sox2), which was not altered by\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    treatment. Western analysis revealed hyperacetylation of histone H3 proteins in C17.2 cells after\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    treatment for 24\u00a0hr or 48\u00a0hr, suggesting involvement of an epigenetic mechanism in the observed gene induction by this drug. These findings support a role for\n                    <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\n                    in modulating neurotrophic and differentiation factor expression, in keeping with its reported neuroprotective and neurodevelopmental effects.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.12201","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T06:36:03Z","timestamp":1390804563000},"page":"216-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Induction of Neurotrophic and Differentiation Factors in Neural Stem Cells by Valproic Acid"],"prefix":"10.1111","volume":"115","author":[{"given":"Walaa","family":"Almutawaa","sequence":"first","affiliation":[{"name":"Department of Psychiatry &amp; Behavioural Neurosciences McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na Hyea","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioural Neurosciences McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioural Neurosciences McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennard P.","family":"Niles","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioural Neurosciences McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3379"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2012.691478"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.01.004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1508"},{"key":"e_1_2_6_6_1","first-page":"1","article-title":"Valproic acid up\u2010regulates melatonin MT1 and MT2 receptors and neurotrophic factors CDNF and MANF in the rat brain","volume":"16","author":"Niles LP","year":"2012","journal-title":"Int J Neuropsychopharmacol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407643101"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467210902010095"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2011.00702.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005512"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00037-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-5-41"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00587.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90204-P"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.04.058"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(11)70045-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100871"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-007-9212-7"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00794.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.356345"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-013-0042-4"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.3146"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0274"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.05.007"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2010.01400.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03457.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0267"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.3340\/jkns.2013.54.1.8"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145708009024"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.09.019"}],"container-title":["Basic &amp; 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