{"title":"Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice","authors":"","doi":"10.1016/j.ejphar.2024.177096","DOIUrl":null,"url":null,"abstract":"<div><div>The novel antidepressant arketamine, the (<em>R</em>)-enantiomer of ketamine, has been shown to ameliorate demyelination and facilitate remyelination in the brains of cuprizone (CPZ)-treated mice. However, the mechanisms behind its effects remain unclear. Given the role of transforming growth factor β1 (TGF-β1) in arketamine's antidepressant-like effects, we examined whether TGF-β1 also plays a role in arketamine's effects on demyelination and remyelination in CPZ-treated mice. Additionally, we investigated the effects of intranasal TGF-β1 on demyelination and remyelination in these mice. Repeated intermittent administration of arketamine (10 mg/kg/day, twice weekly for the last 2-weeks) attenuated demyelination in the corpus callosum (CC) of CPZ (6 weeks)-treated mice. Furthermore, pretreatment with RepSox (10 mg/kg/day), an inhibitor of the TGF-β receptor 1, significantly blocked the beneficial effects of arketamine on the demyelination in the CC of CPZ-treated mice. Additionally, repeated intermittent administration of TGF-β1 (3.0 μg/kg/day, twice weekly for 2 weeks) significantly ameliorated demyelination and facilitated remyelination in the CC of CPZ-treated mice. These data suggest that arketamine can mitigate demyelination and facilitates remyelination in the brains of CPZ-treated mice through a TGF-β1-dependent mechanism.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299924007866","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
The novel antidepressant arketamine, the (R)-enantiomer of ketamine, has been shown to ameliorate demyelination and facilitate remyelination in the brains of cuprizone (CPZ)-treated mice. However, the mechanisms behind its effects remain unclear. Given the role of transforming growth factor β1 (TGF-β1) in arketamine's antidepressant-like effects, we examined whether TGF-β1 also plays a role in arketamine's effects on demyelination and remyelination in CPZ-treated mice. Additionally, we investigated the effects of intranasal TGF-β1 on demyelination and remyelination in these mice. Repeated intermittent administration of arketamine (10 mg/kg/day, twice weekly for the last 2-weeks) attenuated demyelination in the corpus callosum (CC) of CPZ (6 weeks)-treated mice. Furthermore, pretreatment with RepSox (10 mg/kg/day), an inhibitor of the TGF-β receptor 1, significantly blocked the beneficial effects of arketamine on the demyelination in the CC of CPZ-treated mice. Additionally, repeated intermittent administration of TGF-β1 (3.0 μg/kg/day, twice weekly for 2 weeks) significantly ameliorated demyelination and facilitated remyelination in the CC of CPZ-treated mice. These data suggest that arketamine can mitigate demyelination and facilitates remyelination in the brains of CPZ-treated mice through a TGF-β1-dependent mechanism.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.