{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T17:28:11Z","timestamp":1764350891920,"version":"3.41.2"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33NS109441"],"award-info":[{"award-number":["R33NS109441"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Vanishing white matter (VWM) is a devastating autosomal recessive leukodystrophy, resulting in neurological deterioration and premature death, and without curative treatment. Pathogenic hypomorphic variants in subunits of the eukaryotic initiation factor 2B (eIF2B) cause VWM. eIF2B is required for regulating the integrated stress response (ISR), a physiological response to cellular stress. In patients\u2019 central nervous system, reduced eIF2B activity causes deregulation of the ISR. In VWM mouse models, the extent of ISR deregulation correlates with disease severity. One approach to restoring eIF2B activity is by inhibition of GSK3\u03b2, a kinase that phosphorylates eIF2B and reduces its activity. Lithium, an inhibitor of GSK3\u03b2, is thus expected to stimulate eIF2B activity and ameliorate VWM symptoms. The effects of lithium were tested in zebrafish and mouse VWM models. Lithium improved motor behavior in homozygous <jats:italic>eif2b5<\/jats:italic> mutant zebrafish. In lithium-treated <jats:italic>2b4<jats:sup>he<\/jats:sup>2b5<jats:sup>ho<\/jats:sup><\/jats:italic> mutant mice, a paradoxical increase in some ISR transcripts was found. Furthermore, at the dosage tested, lithium induced significant polydipsia in both healthy controls and <jats:italic>2b4<jats:sup>he<\/jats:sup>2b5<jats:sup>ho<\/jats:sup><\/jats:italic> mutant mice and did not increase the expression of other markers of lithium efficacy. In conclusion, lithium is not a drug of choice for further development in VWM based on the limited or lack of efficacy and significant side-effect profile.<\/jats:p>","DOI":"10.3389\/fnins.2024.1275744","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T04:12:24Z","timestamp":1706587944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Lithium: effects in animal models of vanishing white matter are not promising"],"prefix":"10.3389","volume":"18","author":[{"given":"Diede","family":"Witkamp","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Oudejans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leoni","family":"Hoogterp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gino V.","family":"Hu-A-Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn A.","family":"Glaittli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara J.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marleen","family":"Huijsmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Truus E. 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Transl. Neurol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0092-8674(02)01015-2","article-title":"\u03b2-Catenin and Tcf mediate cell positioning in the intestinal epithelium by controlling the expression of EphB\/ephrinB","volume":"111","author":"Batlle","year":"2002","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2165\/00002018-199921060-00002","article-title":"Drug-induced diabetes insipidus","volume":"21","author":"Bendz","year":"1999","journal-title":"Drug Saf."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.pharmthera.2014.11.016","article-title":"Glycogen synthase kinase-3 (Gsk3): regulation, actions, and diseases","volume":"148","author":"Beurel","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1083\/jcb.200311021","article-title":"Sox9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the Cdx2 and Muc2 genes","volume":"166","author":"Blache","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/NEN.0b013e318203ae74","article-title":"Defective glial maturation in vanishing white matter disease","volume":"70","author":"Bugiani","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1111\/j.1601-183X.2011.00682.x","article-title":"Antidepressant-like responses to lithium in genetically diverse mouse strains","volume":"10","author":"Can","year":"2011","journal-title":"Genes Brain Behav."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/\u03b2-catenin signaling in development and disease","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/jmd2.12258","article-title":"Chronic lithium administration in a mouse model for Krabbe disease","volume":"63","author":"Del Grosso","year":"2022","journal-title":"JIMD Rep."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1242\/jcs.00384","article-title":"Gsk-3: tricks of the trade for a multi-tasking kinase","volume":"116","author":"Doble","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1172\/JCI83908","article-title":"Astrocytes are central in the pathomechanisms of vanishing white matter","volume":"126","author":"Dooves","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/nn.2855","article-title":"Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination","volume":"14","author":"Fancy","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref14","first-page":"1","volume-title":"Analysis of variance\u2014Why it is more important than ever","author":"Gelman","year":"2005"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e0124956","DOI":"10.1371\/journal.pone.0124956","article-title":"Transcription factor Creb3L1 regulates endoplasmic reticulum stress response genes in the osmotically challenged rat hypothalamus","volume":"10","author":"Greenwood","year":"2015","journal-title":"PLoS One"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1093\/brain\/awx074","article-title":"Repurposed drugs targeting eif2\u03b1-P-mediated translational repression prevent neurodegeneration in mice","volume":"140","author":"Halliday","year":"2017","journal-title":"Brain"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1002\/ana.25287","article-title":"The natural history of vanishing white matter","volume":"84","author":"Hamilton","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ncb2738","article-title":"Er-stress-induced transcriptional regulation increases protein synthesis leading to cell death","volume":"15","author":"Han","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/S1097-2765(00)00108-8","article-title":"Regulated translation initiation controls stress-induced gene expression in mammalian cells","volume":"6","author":"Harding","year":"","journal-title":"Mol. Cell"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/S1097-2765(00)80330-5","article-title":"Perk is essential for translational regulation and cell survival during the unfolded protein response","volume":"5","author":"Harding","year":"","journal-title":"Mol. 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Biol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e56319","DOI":"10.7554\/eLife.56319","article-title":"Vanishing white matter disease expression of truncated Eif2B5 activates induced stress response","volume":"9","author":"Keefe","year":"2020","journal-title":"Elife"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"540","DOI":"10.4097\/kjae.2015.68.6.540","article-title":"T test as a parametric statistic","volume":"68","author":"Kim","year":"2015","journal-title":"Korean J. Anesthesiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3402","DOI":"10.1016\/S0021-9258(18)32875-8","article-title":"Purification of the eukaryotic initiation factor 2-eukaryotic initiation factor 2B complex and characterization of its guanine nucleotide exchange activity during protein synthesis initiation","volume":"258","author":"Konieczny","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ab.2003.10.047","article-title":"Visible fluorescent detection of proteins in polyacrylamide gels without staining","volume":"326","author":"Ladner","year":"2004","journal-title":"Anal. Biochem."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2699","DOI":"10.1007\/s11517-023-02875-2","article-title":"A transfer learning approach on Mri-based radiomics signature for overall survival prediction of low-grade and high-grade gliomas","volume":"61","author":"Le","year":"2023","journal-title":"Med. Biol. Eng. Comput."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3233\/JAD-2010-1276","article-title":"Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology","volume":"19","author":"Leroy","year":"2010","journal-title":"J. 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A."},{"key":"ref36","doi-asserted-by":"crossref","DOI":"10.1002\/9780470479216.corpsy0524","article-title":"Mann-Whitney U test","volume-title":"The Corsini Encyclopedia of Psychology","author":"Mcknight","year":"2010"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.yexcr.2011.02.012","article-title":"Glycogen synthase kinase-3 regulates endoplasmic reticulum (Er) stress-induced Chop expression in neuronal cells","volume":"317","author":"Meares","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/nrm3470","article-title":"The complex world of Wnt receptor signalling","volume":"13","author":"Niehrs","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"6791","DOI":"10.1523\/JNEUROSCI.4753-03.2004","article-title":"Glycogen synthase kinase-3\u03b2 haploinsufficiency mimics the behavioral and molecular effects of lithium","volume":"24","author":"O\u2019brien","year":"2004","journal-title":"J. Neurosci."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.15252\/embr.201642195","article-title":"The integrated stress response","volume":"17","author":"Pakos-Zebrucka","year":"2016","journal-title":"EMBO Rep."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/j.bbamcr.2013.04.004","article-title":"Interplay between Sox9, \u03b2-catenin and Ppar\u03b3 activation in colorectal cancer","volume":"1833","author":"Panza","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1128\/MCB.22.2.578-586.2002","article-title":"Role of translation initiation factor 2B in control of cell survival by the phosphatidylinositol 3-kinase\/Akt\/glycogen synthase kinase 3\u03b2 signaling pathway","volume":"22","author":"Pap","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1097\/FBP.0b013e32833da5da","article-title":"Intracellular pathways underlying the effects of lithium","volume":"21","author":"Pasquali","year":"2010","journal-title":"Behav. Pharmacol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1042\/BST0331487","article-title":"eif2B, a mediator of general and gene-specific translational control","volume":"33","author":"Pavitt","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e1491","DOI":"10.1002\/wrna.1491","article-title":"Regulation of translation initiation factor eif2B at the hub of the integrated stress response","volume":"9","author":"Pavitt","year":"2018","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"45e","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time Rt-Pcr","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1080\/17482960902803440","article-title":"Treatment with lithium carbonate does not improve disease progression in two different strains of Sod1 mutant mice","volume":"10","author":"Pizzasegola","year":"2009","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/978-3-642-56688-2_4","article-title":"Regulation of eukaryotic initiation factor eif2B","volume":"26","author":"Proud","year":"2001","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e93031","DOI":"10.1371\/journal.pone.0093031","article-title":"An extended \u0394ct-method facilitating normalisation with multiple reference genes suited for quantitative Rt-Pcr analyses of human hepatocyte-like cells","volume":"9","author":"Riedel","year":"2014","journal-title":"PLoS One"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1176\/appi.ajp-rj.2017.120202","article-title":"Lithium in child and adolescent bipolar disorder","volume":"12","author":"Rosen","year":"2017","journal-title":"Am. J. Psych. Resid. J."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1039\/C7MT00203C","article-title":"From direct to indirect lithium targets: a comprehensive review of omics data","volume":"9","author":"Roux","year":"2017","journal-title":"Metallomics"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1742-4690-3-2","article-title":"Factor correction as a tool to eliminate between-session variation in replicate experiments: application to molecular biology and retrovirology","volume":"3","author":"Ruijter","year":"2006","journal-title":"Retrovirology"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1101\/gad.287404","article-title":"Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration","volume":"18","author":"Sansom","year":"2004","journal-title":"Genes Dev."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time Pcr data by the comparative Ct method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1399-5618.2009.00706.x","article-title":"The history of lithium therapy","volume":"11","author":"Shorter","year":"2009","journal-title":"Bipolar Disord."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1016\/S0960-9822(02)70790-2","article-title":"Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells","volume":"6","author":"Stambolic","year":"1996","journal-title":"Curr. Biol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"a007898","DOI":"10.1101\/cshperspect.a007898","article-title":"The \u03b2-catenin destruction complex","volume":"5","author":"Stamos","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1691\/ph.2014.4672","article-title":"Effect of lithium chloride on endoplasmic reticulum stress-related perk\/rock signaling in a rat model of glaucoma","volume":"69","author":"Sun","year":"2014","journal-title":"Pharmazie"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"105494","DOI":"10.1016\/j.parkreldis.2023.105494","article-title":"Development and validation of the Vietnamese smell identification test","volume":"113","author":"Tran","year":"2023","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1074\/jbc.M111.323337","article-title":"Adenomatous polyposis coli (Apc) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (Gsk-3) activity","volume":"287","author":"Valvezan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/ana.10112","article-title":"Mutations in each of the five subunits of translation initiation factor eif2B can cause leukoencephalopathy with vanishing white matter","volume":"51","author":"Van Der Knaap","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.nbd.2005.08.009","article-title":"Regulation of protein synthesis in lymphoblasts from vanishing white matter patients","volume":"21","author":"Van Kollenburg","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref63","article-title":"Lithium treatment over the lifespan in bipolar disorders","volume":"11","author":"Volkmann","year":"2020","journal-title":"Front. Psych."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0014-5793(97)01548-2","article-title":"Regulation of eukaryotic initiation factor eif2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin","volume":"421","author":"Welsh","year":"1998","journal-title":"FEBS Lett."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3389\/fncel.2017.00411","article-title":"Proteomic and metabolomic analyses of vanishing white matter mouse astrocytes reveal deregulation of Er functions","volume":"11","author":"Wisse","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1002\/acn3.51611","article-title":"Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1","volume":"9","author":"Witkamp","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"e42940","DOI":"10.7554\/eLife.42940","article-title":"eif2B activator prevents neurological defects caused by a chronic integrated stress response","volume":"8","author":"Wong","year":"2019","journal-title":"Elife"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1096\/fj.13-243329","article-title":"Analysis of the subunit organization of the eif2B complex reveals new insights into its structure and regulation","volume":"28","author":"Wortham","year":"2014","journal-title":"FASEB J."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.tibs.2009.10.002","article-title":"Gsk3: a multifaceted kinase in Wnt signaling","volume":"35","author":"Wu","year":"2010","journal-title":"Trends Biochem. 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