Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY European journal of pharmacology Pub Date : 2024-11-03 DOI:10.1016/j.ejphar.2024.177096
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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.
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转化生长因子-β1介导了阿克他敏对铜绿素处理过的小鼠大脑脱髓鞘和再髓鞘化的有益影响。
氯胺酮的(R)-对映体--新型抗抑郁剂阿克他敏已被证明能改善铜绿酸(CPZ)处理过的小鼠大脑中的脱髓鞘现象并促进其再髓鞘化。然而,其作用背后的机制仍不清楚。鉴于转化生长因子β1(TGF-β1)在阿卡他敏的抗抑郁样作用中的作用,我们研究了TGF-β1是否也在阿卡他敏对CPZ治疗小鼠脱髓鞘和再髓鞘化的影响中发挥作用。此外,我们还研究了鼻内 TGF-β1 对这些小鼠脱髓鞘和再髓鞘化的影响。在CPZ(6周)治疗小鼠的胼胝体(CC)中,反复间歇给予阿克他敏(10毫克/千克/天,每周两次,持续2周)可减轻脱髓鞘。此外,用TGF-β受体1抑制剂RepSox(10毫克/千克/天)进行预处理可显著阻断阿克拉明对CPZ治疗小鼠胼胝体脱髓鞘的有益影响。此外,反复间歇性给予 TGF-β1(3.0 μg/kg/天,每周两次,持续 2 周)可明显改善 CPZ 治疗小鼠 CC 的脱髓鞘并促进其再髓鞘化。这些数据表明,通过TGF-β1依赖性机制,开塞露可减轻CPZ治疗小鼠大脑的脱髓鞘并促进其再髓鞘化。
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来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
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.
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