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.
2 papers in the library · 19 citations · publishing 2024-2025
Arketamine, the (R)-enantiomer of ketamine, reduces damage to the myelin sheath and promotes its repair in the brains of mice treated with cuprizone, a chemical that induces demyelination. The beneficial effects occur through a mechanism dependent on transforming growth factor β1 (TGF-β1). Blocking the TGF-β1 receptor with RepSox prevented arketamine's protective effects. Directly administering TGF-β1 intranasally also reduced demyelination and enhanced remyelination in the corpus callosum. These findings suggest that arketamine's effects on myelin repair rely on TGF-β1 signaling, pointing to potential therapeutic targets for demyelinating diseases like multiple sclerosis.
Postoperative cognitive dysfunction (POCD) involves declines in memory, attention, and executive abilities after surgery, with no effective drugs available. In a mouse model of POCD, a single injection of arketamine (10 mg/kg) improved cognitive function and reduced demyelination in the corpus callosum. Blocking TGF-β receptor 1 with RepSox (10 mg/kg) prevented these benefits, while intranasal TGF-β1 (3.0 μg/kg) alone alleviated cognitive impairments and demyelination. The findings indicate arketamine acts through a TGF-β1-dependent mechanism, suggesting it as a potential treatment for POCD.