{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:45:16Z","timestamp":1792547116209,"version":"4.5.0"},"reference-count":78,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology Reports"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.toxrep.2025.101974","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T16:44:08Z","timestamp":1740761048000},"page":"101974","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Betaine alleviates deficits in motor behavior, neurotoxic effects, and neuroinflammatory responses in a rat model of demyelination"],"prefix":"10.1016","volume":"14","author":[{"given":"Amina E.","family":"Essawy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gihad Jamal","family":"Bekheet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherine","family":"Abdel Salam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem Hasaballah","family":"Alhasani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba-Tallah Abd Elrahim","family":"Abd Elkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxrep.2025.101974_bib1","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s10753-021-01447-6","article-title":"Neuroprotective effects of telmisartan and nifedipine against cuprizone-induced demyelination and behavioral dysfunction in mice: roles of NF-\u03baB and Nrf2","volume":"44","author":"Abd El Aziz","year":"2021","journal-title":"Inflam"},{"key":"10.1016\/j.toxrep.2025.101974_bib2","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1007\/s12035-020-01972-9","article-title":"Repurposing of secukinumab as neuroprotective in cuprizone-induced multiple sclerosis experimental model via inhibition of oxidative, inflammatory, and neurodegenerative signaling","volume":"57","author":"Abdel-Maged","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.toxrep.2025.101974_bib3","first-page":"266","article-title":"Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination","volume":"65","author":"Acs","year":"2012","journal-title":"Ideggyogy. Sz."},{"key":"10.1016\/j.toxrep.2025.101974_bib4","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22115904","article-title":"Astrocytes in multiple sclerosis\u2014Essential constituents with diverse multifaceted functions","volume":"22","author":"Aharoni","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/bs12030070","article-title":"Biochanin A improves memory decline and brain pathology in cuprizone-induced mouse model of multiple sclerosis","volume":"12","author":"Aldhahri","year":"2022","journal-title":"Behav. Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10989-012-9297-9","article-title":"Antioxidant defense of betaine against oxidative stress induced by ethanol in the rat testes","volume":"18","author":"Alirezaei","year":"2012","journal-title":"Int. J. Pept. Res. Ther."},{"key":"10.1016\/j.toxrep.2025.101974_bib7","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s13105-011-0107-1","article-title":"Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum","volume":"67","author":"Alirezaei","year":"2011","journal-title":"J. Physiol. Biochem."},{"key":"10.1016\/j.toxrep.2025.101974_bib8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s12576-015-0360-0","article-title":"Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa\/benserazide in the brain of rats","volume":"65","author":"Alirezaei","year":"2015","journal-title":"J. Physiol. Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib9","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10989-012-9300-5","article-title":"Betaine elevates ovarian antioxidant enzyme activities and demonstrates methyl donor effect in non-pregnant rats","volume":"18","author":"Alirezaei","year":"2012","journal-title":"Int. J. Pept. Res. Ther."},{"key":"10.1016\/j.toxrep.2025.101974_bib10","doi-asserted-by":"crossref","DOI":"10.3390\/biology10060456","article-title":"Beneficial effects of betaine: A Comprehensive review","volume":"10","author":"Arumugam","year":"2021","journal-title":"Biol"},{"key":"10.1016\/j.toxrep.2025.101974_bib11","doi-asserted-by":"crossref","DOI":"10.4103\/ijpvm.IJPVM_108_19","article-title":"Preventive effect of Ferula asafoetida oleo gum resin on histopathology in cuprizone-induced demyelination mice","volume":"11","author":"Bagheri","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"10.1016\/j.toxrep.2025.101974_bib12","first-page":"122","article-title":"The potential therapeutic effect of adipose tissue-derived mesenchymal stem cell transplantation on cuprizone model of multiple sclerosis in the mice","volume":"43","author":"Barkat","year":"2020","journal-title":"Egypt J. Histol."},{"key":"10.1016\/j.toxrep.2025.101974_bib13","first-page":"882","article-title":"Improved method for the determination of blood glutathione","volume":"61","author":"Beutler","year":"1963","journal-title":"J. Lab. Clin. Med"},{"key":"10.1016\/j.toxrep.2025.101974_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2018.03.020","article-title":"Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice","volume":"320","author":"B\u00f6lcskei","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.toxrep.2025.101974_bib15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.bbr.2017.05.045","article-title":"Increased central dopaminergic activity might be involved in the behavioral abnormality of cuprizone exposure mice","volume":"331","author":"Chang","year":"2017","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuroinflammation and M2 microglia: The good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.toxrep.2025.101974_bib17","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0007754","article-title":"What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach","volume":"4","author":"Chomiak","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.toxrep.2025.101974_bib18","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.cpr.2012.09.007","article-title":"The biomedical model of mental disorder: a critical analysis of its validity, utility, and effects on psychotherapy research","volume":"33","author":"Deacon","year":"2013","journal-title":"Clin. Psychol. Rev."},{"key":"10.1016\/j.toxrep.2025.101974_bib19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pathophys.2010.04.004","article-title":"The relevance of animal models in multiple sclerosis research","volume":"18","author":"Denic","year":"2011","journal-title":"Pathophysiol"},{"key":"10.1016\/j.toxrep.2025.101974_bib20","doi-asserted-by":"crossref","first-page":"280","DOI":"10.5603\/FM.a2021.0044","article-title":"N-acetylcysteine protects against cuprizone-induced demyelination: Histological and immunohistochemical study","volume":"81","author":"El Sharouny","year":"2022","journal-title":"Folia Morphol. (Warsz. )"},{"key":"10.1016\/j.toxrep.2025.101974_bib21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.taap.2018.05.035","article-title":"Neuroprotective effect of linagliptin against cuprizone-induced demyelination and behavioural dysfunction in mice: A pivotal role of AMPK\/SIRT1 and JAK2\/STAT3\/NF-\u03baB signalling pathway modulation","volume":"352","author":"Elbaz","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.toxrep.2025.101974_bib22","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23158658","article-title":"Dual mechanism of action of curcumin in experimental models of multiple sclerosis","volume":"23","author":"ELBini-Dhouib","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib23","doi-asserted-by":"crossref","first-page":"48573","DOI":"10.1007\/s11356-022-19251-6","article-title":"Anti-kindling effect of Ginkgo biloba leaf extract and L-carnitine in the pentylenetetrazol model of epilepsy","volume":"29","author":"Essawy","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1515\/tjb-2016-0183","article-title":"Betaine treatment decreased serum glucose and lipid levels, hepatic and renal oxidative stress in streptozotocin-induced diabetic rats","volume":"43","author":"Evran","year":"2018","journal-title":"Turk. J. Biochem."},{"key":"10.1016\/j.toxrep.2025.101974_bib25","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/acn3.207","article-title":"Aggregation of MBP in chronic demyelination","volume":"2","author":"Frid","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.toxrep.2025.101974_bib26","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s11033-009-9508-4","article-title":"Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats","volume":"37","author":"Ganesan","year":"2010","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.toxrep.2025.101974_bib27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0750-0","article-title":"Spatio-temporal profile, phenotypic diversity, and fate of recruited monocytes into the post-ischemic brain","volume":"13","author":"Garcia-Bonilla","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.toxrep.2025.101974_bib28","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1007\/s12035-016-9891-5","article-title":"Resveratrol promotes remyelination in cuprizone model of multiple sclerosis: Biochemical and histological study","volume":"54","author":"Ghaiad","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.toxrep.2025.101974_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2013.00045","article-title":"Origin and differentiation of microglia","volume":"7","author":"Ginhoux","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.toxrep.2025.101974_bib30","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s12031-015-0595-5","article-title":"Anatomical distribution of cuprizone-induced lesions in C57BL6 mice","volume":"57","author":"Goldberg","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.toxrep.2025.101974_bib31","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s00415-016-8114-3","article-title":"The role of global and regional gray matter volume decrease in multiple sclerosis","volume":"263","author":"Grothe","year":"2016","journal-title":"J. Neurol."},{"key":"10.1016\/j.toxrep.2025.101974_bib32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2014.00073","article-title":"Glial response during cuprizone-induced de- and remyelination in the CNS: Lessons learned","volume":"8","author":"Gudi","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.toxrep.2025.101974_bib33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.brainresbull.2017.09.007","article-title":"The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation","volume":"135","author":"Hashimoto","year":"2017","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.toxrep.2025.101974_bib34","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0278-6915(03)00196-0","article-title":"Betaine in sub-acute and sub-chronic rat studies","volume":"41","author":"Hayes","year":"2003","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.toxrep.2025.101974_bib35","first-page":"142","article-title":"Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone model of multiple sclerosis","volume":"15","author":"Hedayatpour","year":"2013","journal-title":"Cell. J. (Yakhteh)"},{"key":"10.1016\/j.toxrep.2025.101974_bib36","doi-asserted-by":"crossref","DOI":"10.1042\/AN20090032","article-title":"Cuprizone demyelination of the corpus callosum in mice correlates with altered social interaction and impaired bilateral sensorimotor coordination","volume":"1","author":"Hibbits","year":"2009","journal-title":"ASN Neuro"},{"key":"10.1016\/j.toxrep.2025.101974_bib37","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/ajpgi.00332.2012","article-title":"Osmotic regulation of hepatic betaine metabolism","volume":"304","author":"Hoffmann","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.toxrep.2025.101974_bib38","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1007\/s11064-022-03622-z","article-title":"Preventive effect of betaine against cognitive impairments in amyloid \u03b2 peptide-injected mice through sirtuin1 in hippocampus","volume":"47","author":"Ibi","year":"2022","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.arres.2023.100084","article-title":"Betaine intervention as a novel approach to preventing doxorubicin-induced cardiotoxicity","volume":"9","author":"Jaiswal","year":"2023","journal-title":"Adv. Redox Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib40","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18102135","article-title":"Microglia and monocytes\/macrophages polarization reveal novel therapeutic mechanism against stroke","volume":"18","author":"Kanazawa","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib41","doi-asserted-by":"crossref","first-page":"8284","DOI":"10.1523\/JNEUROSCI.0841-12.2012","article-title":"IL-17-induced Act1-mediated signaling is critical for cuprizone-induced demyelination","volume":"32","author":"Kang","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.toxrep.2025.101974_bib42","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.biopha.2018.04.154","article-title":"Betaine protects mice against acetaminophen hepatotoxicity possibly via mitochondrial complex II and glutathione availability","volume":"103","author":"Khodayar","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.toxrep.2025.101974_bib43","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1080\/09168451.2016.1240604","article-title":"Choline and betaine ameliorate liver lipid accumulation induced by vitamin B deficiency in rats","volume":"81","author":"Kitagawa","year":"2017","journal-title":"Biosc. Biotech. Biochem."},{"key":"10.1016\/j.toxrep.2025.101974_bib44","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1007\/s11064-017-2397-3","article-title":"Betaine in the brain: Characterization of betaine uptake, its influence on other osmolytes and its potential role in neuroprotection from osmotic stress","volume":"42","author":"Knight","year":"2017","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib45","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/jcmm.13034","article-title":"Macrophage polarization: a key event in the secondary phase of acute spinal cord injury","volume":"21","author":"Kong","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.toxrep.2025.101974_bib46","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10735-019-09824-0","article-title":"Oligoprotective effect of metformin through the AMPK-dependent on restoration of mitochondrial hemostasis in the cuprizone-induced multiple sclerosis model","volume":"50","author":"Largani","year":"2019","journal-title":"J. Mol. Histol."},{"key":"10.1016\/j.toxrep.2025.101974_bib47","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1152\/jn.00400.2021","article-title":"Betaine protects rats against ischemia\/reperfusion injury-induced brain damage","volume":"127","author":"Li","year":"2022","journal-title":"J. Neurophysiol."},{"key":"10.1016\/j.toxrep.2025.101974_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.mehy.2019.109356","article-title":"A diet rich in taurine, cysteine, folate, B12 and betaine may lessen risk for Alzheimer's disease by boosting brain synthesis of hydrogen sulfide","volume":"132","author":"McCarty","year":"2019","journal-title":"Med. Hypotheses"},{"key":"10.1016\/j.toxrep.2025.101974_bib49","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s00401-019-01992-3","article-title":"The origin, fate, and contribution of macrophages to spinal cord injury pathology","volume":"137","author":"Milich","year":"2019","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.toxrep.2025.101974_bib50","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1007\/s10787-022-01045-4","article-title":"Nebivolol elicits a neuroprotective effect in the cuprizone model of multiple sclerosis in mice: emphasis on M1\/M2 polarization and inhibition of NLRP3 inflammasome activation","volume":"30","author":"Naeem","year":"2022","journal-title":"Inflammopharmacol"},{"key":"10.1016\/j.toxrep.2025.101974_bib51","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.neuroscience.2008.06.046","article-title":"Microglial clearance function in health and disease","volume":"158","author":"Napoli","year":"2009","journal-title":"Neurosci"},{"key":"10.1016\/j.toxrep.2025.101974_bib52","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.toxrep.2025.101974_bib53","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ebiom.2019.05.062","article-title":"Investigation of betaine as a novel psychotherapeutic for schizophrenia","volume":"45","author":"Ohnishi","year":"2019","journal-title":"EBioMed"},{"key":"10.1016\/j.toxrep.2025.101974_bib54","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5115\/acb.2018.51.2.119","article-title":"Ameliorative effects of Moringa on cuprizone-induced memory decline in rat model of multiple sclerosis","volume":"51","author":"Omotoso","year":"2018","journal-title":"Anat. Cell. Biol."},{"key":"10.1016\/j.toxrep.2025.101974_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2019.e02102","article-title":"Cuprizone toxicity and Garcinia kola biflavonoid complex activity on hippocampal morphology and neurobehaviour","volume":"5","author":"Omotoso","year":"2019","journal-title":"Heliyon"},{"key":"10.1016\/j.toxrep.2025.101974_bib56","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.pathophys.2018.04.004","article-title":"Kolaviron protects the brain in cuprizone-induced model of experimental multiple sclerosis via enhancement of intrinsic antioxidant mechanisms: Possible therapeutic applications?","volume":"25","author":"Omotoso","year":"2018","journal-title":"Pathophysiol"},{"key":"10.1016\/j.toxrep.2025.101974_bib57","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.3390\/brainsci3031282","article-title":"Myelin recovery in multiple sclerosis: The challenge of remyelination","volume":"3","author":"Podbielska","year":"2013","journal-title":"Brain Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib58","article-title":"The rotarod","volume":"42","author":"Pritchett","year":"2003","journal-title":"Contemp. Top. Lab. Anim. Sci."},{"key":"10.1016\/j.toxrep.2025.101974_bib59","first-page":"1","volume":"2018","author":"Product monograph","year":"2018","journal-title":"Betaine anhydrous Powder Oral. Solut., Rec. rare Dis. Can. Inc."},{"key":"10.1016\/j.toxrep.2025.101974_bib60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2021.09.023","article-title":"The emerging tale of microglia in psychiatric disorders","volume":"131","author":"Rahimian","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.toxrep.2025.101974_bib61","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.768076","article-title":"Regulation of peripheral inflammation by a non-viable, non-colonizing strain of commensal bacteria","volume":"13","author":"Ramani","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.toxrep.2025.101974_bib62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.116.237503","article-title":"Oxidative stress and the central nervous system","volume":"360","author":"Salim","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.toxrep.2025.101974_bib63","series-title":"Nutritional Epigenomics","first-page":"319","article-title":"Chapter 19 - B-vitamins & one-carbon metabolism: Impacts on the epigenome during development, in: B.S. Ferguson (Ed","author":"Sant","year":"2019"},{"key":"10.1016\/j.toxrep.2025.101974_bib64","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neubiorev.2019.08.008","article-title":"Behavioural phenotypes in the cuprizone model of central nervous system demyelination","volume":"107","author":"Sen","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.toxrep.2025.101974_bib65","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/tox.22664","article-title":"Role of betaine in liver injury induced by the exposure to ionizing radiation","volume":"34","author":"Shedid","year":"2019","journal-title":"Environ. Toxicol."},{"key":"10.1016\/j.toxrep.2025.101974_bib66","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s10571-020-00910-6","article-title":"Mesenchymal stem cells ameliorate cuprizone-induced demyelination by targeting oxidative stress and mitochondrial dysfunction","volume":"41","author":"Shiri","year":"2021","journal-title":"Cell. Mol. Neurobiol."},{"key":"10.1016\/j.toxrep.2025.101974_bib67","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1021\/acs.biochem.6b01072","article-title":"Cuprizone intoxication induces cell intrinsic alterations in oligodendrocyte metabolism independent of copper chelation","volume":"56","author":"Taraboletti","year":"2017","journal-title":"Biochem"},{"key":"10.1016\/j.toxrep.2025.101974_bib68","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1021\/acschemneuro.2c00380","article-title":"Betaine attenuates chronic constriction injury-induced neuropathic pain in rats by inhibiting KIF17-mediated nociception","volume":"13","author":"Tiwari","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.toxrep.2025.101974_bib69","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10545-010-9088-4","article-title":"Choline and betaine in health and disease","volume":"34","author":"Ueland","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.toxrep.2025.101974_bib70","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1136\/jim-2016-000339","article-title":"Update on disease-modifying therapies for multiple sclerosis","volume":"65","author":"Vargas","year":"2017","journal-title":"J. Investig. Med."},{"key":"10.1016\/j.toxrep.2025.101974_bib71","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2174\/1570159X15666170717120343","article-title":"Five decades of cuprizone, an updated model to replicate demyelinating diseases","volume":"17","author":"Vega-Riquer","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.toxrep.2025.101974_bib72","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1007\/s12035-017-0534-2","article-title":"Maternal folic acid supplementation during pregnancy improves neurobehavioral development in rat offspring","volume":"55","author":"Wang","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.toxrep.2025.101974_bib73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.02670","article-title":"Betaine inhibits interleukin-1\u03b2 production and release: Potential mechanisms","volume":"9","author":"Xia","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.toxrep.2025.101974_bib74","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/jnr.23997","article-title":"Ultrastructural abnormalities and loss of myelinated fibers in the corpus callosum of demyelinated mice induced by cuprizone","volume":"95","author":"Xiu","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib75","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.4049\/jimmunol.1700920","article-title":"Betaine ameliorates experimental autoimmune encephalomyelitis by inhibiting dendritic cell\u2013derived IL-6 production and Th17 differentiation","volume":"200","author":"Yang","year":"2018","journal-title":"J. Immunol."},{"key":"10.1016\/j.toxrep.2025.101974_bib76","first-page":"310","article-title":"Neuroprotective potential of Spirulina platensis against aluminium chloride-induced neural degeneration","volume":"18","author":"Yousef","year":"2020","journal-title":"Curr. Top. Nutraceutical Res."},{"key":"10.1016\/j.toxrep.2025.101974_bib77","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s12031-013-0026-4","article-title":"Cuprizone-induced demyelination as a tool to study remyelination and axonal protection","volume":"51","author":"Zendedel","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.toxrep.2025.101974_bib78","first-page":"1","article-title":"Betaine inhibits NLRP3 inflammasome hyperactivation and regulates microglial M1\/M2 phenotypic differentiation, thereby attenuating lipopolysaccharide-induced depression-like behavior","volume":"2022","author":"Zhang","year":"2022","journal-title":"J. Immunol. Res."}],"container-title":["Toxicology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2214750025000927?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2214750025000927?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:45:20Z","timestamp":1750207520000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2214750025000927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":78,"alternative-id":["S2214750025000927"],"URL":"https:\/\/doi.org\/10.1016\/j.toxrep.2025.101974","relation":{},"ISSN":["2214-7500"],"issn-type":[{"value":"2214-7500","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Betaine alleviates deficits in motor behavior, neurotoxic effects, and neuroinflammatory responses in a rat model of demyelination","name":"articletitle","label":"Article Title"},{"value":"Toxicology Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxrep.2025.101974","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"101974"}}