Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice.
Ming-Ming Zhao, Ting-Ting Zhu, Dan Xu, Xiayun Wan, Guilin Liu, Rumi Murayama, Yi Cai, Yong Yue, Xing-Ming Wang, Jian-Jun Yang, Kenji Hashimoto
European Journal of Pharmacology December 15, 2024 DOI: 10.1016/j.ejphar.2024.177096 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Cuprizone-treated mice |
| Interventions | Arketamine RepSox TGF-β1 |
| Dose | 10 mg/kg/day arketamine, 10 mg/kg/day RepSox, 3.0 μg/kg/day TGF-β1 |
| Duration | 6-week cuprizone treatment; arketamine or TGF-β1 administered twice weekly for the last 2 weeks |
| Topics | Ketamine |
| Keywords | Cuprizone Demyelination Remyelination Tgf-β1 Antidepressants Multiple sclerosis Brain research Drug development |
| Citations | 14 |
| Key findings | Arketamine attenuates demyelination and facilitates remyelination in the corpus callosum of cuprizone-treated mice through a TGF-β1-dependent mechanism. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice. European Journal of Pharmacology March 15, 2025
- Arketamine alleviates cognitive impairments and demyelination in mice with postoperative cognitive dysfunction via TGF-β1 activation. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
- Potential molecular pathways and therapeutic implications of rapid-acting antidepressants on myelin biology: a scoping review. Frontiers in Neuroscience 2025
- Demyelination in psychiatric and neurological disorders: Mechanisms, clinical impact, and novel therapeutic strategies. Neuroscience & Biobehavioral Reviews July 1, 2025
Cites 15
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
- Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine Molecular Psychiatry November 24, 2021
and 10 more in the library