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

Autor: Zhao MM; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Neuroscience Research Institute, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China., Zhu TT; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Neuroscience Research Institute, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China., Xu D; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Wan X; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan., Liu G; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, 266100, China., Murayama R; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan., Cai Y; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan., Yue Y; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan., Wang XM; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Neuroscience Research Institute, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China., Yang JJ; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Neuroscience Research Institute, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China., Hashimoto K; Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: hashimoto@faculty.chiba-u.jp.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Nov 03; Vol. 985, pp. 177096. Date of Electronic Publication: 2024 Nov 03.
DOI: 10.1016/j.ejphar.2024.177096
Abstrakt: 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.
Competing Interests: Declaration of competing interest Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers’ honoraria, consultant fee, or research support from Otsuka. Other authors declare no conflict of interest.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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