{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:13:27Z","timestamp":1790748807986,"version":"4.1.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673413"],"award-info":[{"award-number":["81673413"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872846"],"award-info":[{"award-number":["81872846"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20141335"],"award-info":[{"award-number":["BK20141335"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20151421"],"award-info":[{"award-number":["BK20151421"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2242017K3DN33"],"award-info":[{"award-number":["2242017K3DN33"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2242017K40095"],"award-info":[{"award-number":["2242017K40095"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.nbd.2021.105489","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T11:35:16Z","timestamp":1630064116000},"page":"105489","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis"],"prefix":"10.1016","volume":"158","author":[{"given":"Xinjian","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiurong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangming","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2021.105489_bb0005","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.jchromb.2009.05.050","article-title":"Combined gas chromatographic\/mass spectrometric analysis of cholesterol precursors and plant sterols in cultured cells","volume":"877","author":"Acimovic","year":"2009","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"10.1016\/j.nbd.2021.105489_bb0010","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1161\/01.ATV.0000120374.59826.1b","article-title":"Brain cholesterol: long secret life behind a barrier","volume":"24","author":"Bjorkhem","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.nbd.2021.105489_bb0015","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1016\/S0140-6736(06)69900-5","article-title":"Dementia and white-matter demyelination in young patient with neurosyphilis","volume":"368","author":"Brinar","year":"2006","journal-title":"Lancet."},{"key":"10.1016\/j.nbd.2021.105489_bb0020","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/S1474-4422(08)70259-X","article-title":"Cognitive impairment in multiple sclerosis","volume":"7","author":"Chiaravalloti","year":"2008","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0025","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1503\/jpn.110185","article-title":"Hippocampal abnormalities of glutamate\/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden","volume":"38","author":"de Diego-Adelino","year":"2013","journal-title":"J. Psychiatry Neurosci."},{"key":"10.1016\/j.nbd.2021.105489_bb0030","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","article-title":"Thematic review series: brain lipids.Cholesterol metabolism in the central nervous system during early development and in the mature animal","volume":"45","author":"Dietschy","year":"2004","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.nbd.2021.105489_bb0035","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/ana.22337","article-title":"Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients","volume":"69","author":"Dutta","year":"2011","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0040","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/ana.23860","article-title":"Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors","volume":"73","author":"Dutta","year":"2013","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0045","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.foodchem.2013.03.025","article-title":"Phenolic-rich extract from the Costa Rican guava (Psidium friedrichsthalianum) pulp with antioxidant and anti-inflammatory activity. Potential for COPD therapy","volume":"141","author":"Flores","year":"2013","journal-title":"Food Chem."},{"key":"10.1016\/j.nbd.2021.105489_bb0050","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12883-017-0803-8","article-title":"Anxiety, emotional processing and depression in people with multiple sclerosis","volume":"17","author":"Gay","year":"2017","journal-title":"BMC Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0055","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3389\/fncel.2015.00243","article-title":"Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis","volume":"9","author":"Gentile","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.nbd.2021.105489_bb0060","doi-asserted-by":"crossref","first-page":"7345","DOI":"10.1523\/JNEUROSCI.20-19-07345.2000","article-title":"The human DIMINUTO\/DWARF1 homolog seladin-1 confers resistance to Alzheimer\u2019s disease-associated neurodegeneration and oxidative stress","volume":"20","author":"Greeve","year":"2000","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2021.105489_bb0065","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/j.ajpath.2012.01.018","article-title":"Focal immune-mediated white matter demyelination reveals an age-associated increase in axonal vulnerability and decreased remyelination efficiency","volume":"180","author":"Hampton","year":"2012","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.nbd.2021.105489_bb0070","first-page":"260","article-title":"Novel cationic cholesterol derivative-based liposomes for serum-enhanced delivery of siRNA","volume":"353","author":"Han","year":"2008","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.nbd.2021.105489_bb0075","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/1756285608100325","article-title":"Psychopathology in multiple sclerosis: diagnosis, prevalence and treatment","volume":"2","author":"Haussleiter","year":"2009","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"10.1016\/j.nbd.2021.105489_bb0080","doi-asserted-by":"crossref","first-page":"102904","DOI":"10.1016\/j.msard.2021.102904","article-title":"Depression in multiple sclerosis: is one approach for its management enough?","volume":"51","author":"Jones","year":"2021","journal-title":"Mult Scler Relat Disord."},{"key":"10.1016\/j.nbd.2021.105489_bb0085","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.bbrc.2007.06.116","article-title":"Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-pick type C disease improved by valproic acid, a histone deacetylase inhibitor","volume":"360","author":"Kim","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.nbd.2021.105489_bb0090","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00401-011-0849-4","article-title":"Cholinergic imbalance in the multiple sclerosis hippocampus","volume":"122","author":"Kooi","year":"2011","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2021.105489_bb0095","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.neulet.2008.11.058","article-title":"Demyelination of the hippocampus is prominent in the cuprizone model","volume":"451","author":"Koutsoudaki","year":"2009","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.nbd.2021.105489_bb0100","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1001\/jamapsychiatry.2013.2437","article-title":"Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia","volume":"70","author":"Kraguljac","year":"2013","journal-title":"JAMA Psychiatry."},{"key":"10.1016\/j.nbd.2021.105489_bb0105","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.nbd.2019.05.010","article-title":"Voluntary running wheel attenuates motor deterioration and brain damage in cuprizone-induced demyelination","volume":"129","author":"Mandolesi","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.nbd.2021.105489_bb0110","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1046\/j.1471-4159.2001.00015.x","article-title":"Parameters related to lipid metabolism as markers of myelination in mouse brain","volume":"76","author":"Muse","year":"2001","journal-title":"J. Neurochem."},{"key":"10.1016\/j.nbd.2021.105489_bb0115","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/j.euroneuro.2015.05.005","article-title":"Associations of hippocampal metabolism and regional brain grey matter in neuroleptic-naive ultra-high-risk subjects and first-episode schizophrenia","volume":"25","author":"Nenadic","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"10.1016\/j.nbd.2021.105489_bb0120","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1750-3639.2008.00177.x","article-title":"Substantial archaeocortical atrophy and neuronal loss in multiple sclerosis","volume":"19","author":"Papadopoulos","year":"2009","journal-title":"Brain Pathol."},{"key":"10.1016\/j.nbd.2021.105489_bb0125","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1038\/s41598-018-20343-y","article-title":"Evaluating upper limb impairments in multiple sclerosis by exposure to different mechanical environments","volume":"8","author":"Pellegrino","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2021.105489_bb0130","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1677\/JME-08-0071","article-title":"Neuroprotective effects of the Alzheimer\u2019s disease-related gene seladin-1","volume":"41","author":"Peri","year":"2008","journal-title":"J. Mol. Endocrinol."},{"key":"10.1016\/j.nbd.2021.105489_bb0135","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bbr.2011.01.018","article-title":"Inflammation modulates anxiety in an animal model of multiple sclerosis","volume":"220","author":"Peruga","year":"2011","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.nbd.2021.105489_bb0140","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.neubiorev.2014.10.004","article-title":"Cellular and molecular neuropathology of the cuprizone mouse model: clinical relevance for multiple sclerosis","volume":"47","author":"Praet","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.nbd.2021.105489_bb0145","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/S1474-4422(18)30309-0","article-title":"The hippocampus in multiple sclerosis","volume":"17","author":"Rocca","year":"2018","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0150","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.bbalip.2015.02.010","article-title":"Cholesterol in myelin biogenesis and hypomyelinating disorders","volume":"1851","author":"Saher","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.nbd.2021.105489_bb0155","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.expneurol.2012.02.018","article-title":"Cuprizone-induced demyelination in the rat cerebral cortex and thyroid hormone effects on cortical remyelination","volume":"235","author":"Silvestroff","year":"2012","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0160","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2353\/ajpath.2008.070850","article-title":"Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent","volume":"172","author":"Skripuletz","year":"2008","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.nbd.2021.105489_bb0165","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1750-3639.2009.00271.x","article-title":"Cerebellar cortical demyelination in the murine cuprizone model","volume":"20","author":"Skripuletz","year":"2010","journal-title":"Brain Pathol."},{"key":"10.1016\/j.nbd.2021.105489_bb0170","doi-asserted-by":"crossref","first-page":"8017","DOI":"10.1074\/jbc.RA119.010524","article-title":"Correction of Niemann-pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid","volume":"295","author":"Subramanian","year":"2020","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.nbd.2021.105489_bb0175","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202012695","article-title":"Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation and development of pneumococcal disease","volume":"12","author":"Subramanian","year":"2020","journal-title":"EMBO Mol Med."},{"key":"10.1016\/j.nbd.2021.105489_bb0180","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1600-0404.2008.01036.x","article-title":"The cuprizone model for demyelination","volume":"188","author":"Torkildsen","year":"2008","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"10.1016\/j.nbd.2021.105489_bb0185","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S1474-4422(18)30245-X","article-title":"Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study","volume":"17","author":"Trapp","year":"2018","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.nbd.2021.105489_bb0190","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.brainresbull.2015.04.002","article-title":"NMDA receptor NR2B subunits contribute to PTZ-kindling-induced hippocampal astrocytosis and oxidative stress","volume":"114","author":"Zhu","year":"2015","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.nbd.2021.105489_bb0195","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.freeradbiomed.2016.03.004","article-title":"NADPH oxidase activation is required for pentylenetetrazole kindling-induced hippocampal autophagy","volume":"94","author":"Zhu","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.nbd.2021.105489_bb0200","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3389\/fncel.2017.00377","article-title":"Neuronal nitric oxide synthase contributes to PTZ kindling epilepsy-induced hippocampal endoplasmic reticulum stress and oxidative damage","volume":"11","author":"Zhu","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.nbd.2021.105489_bb0205","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pnpbp.2019.03.020","article-title":"Alteration of GABAergic signaling is associated with anxiety-like behavior in temporal lobe epilepsy mice","volume":"93","author":"Zhu","year":"2019","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996121002382?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996121002382?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:29:40Z","timestamp":1760851780000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996121002382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":41,"alternative-id":["S0969996121002382"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2021.105489","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2021.105489","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"105489"}}