Arketamine alleviates cognitive impairments and demyelination in mice with postoperative cognitive dysfunction via TGF-β1 activation.
Ting-Ting Zhu, Ming-Ming Zhao, Dan Xu, Yi Cai, Guilin Liu, Rumi Murayama, Yong Yue, Jian-Jun Yang, Kenji Hashimoto
Progress in neuro-psychopharmacology & biological psychiatry January 10, 2025 DOI: 10.1016/j.pnpbp.2024.111228 (opens in new tab) via PubMed
Summary
AI-generated from the abstractPostoperative 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.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mouse model of postoperative cognitive dysfunction |
| Interventions | Arketamine RepSox TGF-β1 |
| Dose | 10 mg/kg arketamine, 10 mg/kg RepSox, 3.0 μg/kg TGF-β1 |
| Topics | Ketamine |
| Keywords | Demyelination Postoperative cognitive dysfunction Surgery Tgf-β1 |
| Citations | 5 |
| Key finding | Arketamine ameliorates cognitive deficits and demyelination in POCD mice through a TGF-β1-dependent mechanism. |
Abstract
Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive functions, including memory, attention, and executive abilities, following surgery, with no effective therapeutic drugs currently available. Arketamine, the (R)-enantiomer of ketamine, has shown promise in mitigating cognitive deficits in animal models. In this study, we investigated whether arketamine could ameliorate cognitive deficits in a mouse model of POCD, with a focus on the role of transforming growth factor (TGF)-β1 in its effects. POCD mice displayed cognitive impairments and demyelination in the corpus callosum. A single arketamine injection (10 mg/kg) significantly improved both cognitive function and demyelination in the corpus callosum of POCD mice. Notably, pretreatment with RepSox (10 mg/kg), a TGF-β receptor 1 inhibitor, significantly blocked the beneficial effects of arketamine on cognitive deficits and demyelination. Moreover, intranasal administration of TGF-β1 (3.0 μg/kg) markedly alleviated cognitive impairments and demyelination in POCD mice. These findings suggest that arketamine exerts its effects through a TGF-β1-dependent mechanism, positioning it as a potential therapeutic option for POCD.