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, PR China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao 266100, PR China.
J Affect Disord. 2024 Dec 15;367:745-755. doi: 10.1016/j.jad.2024.08.222. Epub 2024 Sep 3.
Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, the relationship between these depression-like behaviors and demyelination remains unclear. Arketamine, the (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects in CRS-exposed mice.
We examined whether arketamine can improve both depression-like behaviors and demyelination in the brains of CRS-exposed mice. Additionally, we investigated the role of transforming growth factor β1 (TGF-β1) in the beneficial effects of arketamine.
A single dose of arketamine (10 mg/kg) improved both depression-like behavior and demyelination in the corpus callosum of CRS-exposed mice. Correlations were found between depression-like behaviors and demyelination in this region. Furthermore, pretreatment with RepSox, an inhibitor of TGF-β1 receptor, significantly blocked the beneficial effects of arketamine on depression-like behaviors and demyelination in CRS-exposed mice. Finally, a single intranasal administration of TGF-β1 ameliorated both depression-like behaviors and demyelination in CRS-exposed mice.
The precise mechanisms by which TGF-β1 contributes to the effects of arketamine remain unclear.
These data suggest that CRS-induced demyelination in the corpus callosum may contribute to depression-like behaviors, and that arketamine can mitigate these changes through a TGF-β1-dependent mechanism.
慢性束缚应激（CRS）可导致大脑中出现抑郁样行为和脱髓鞘；然而，这些抑郁样行为和脱髓鞘之间的关系尚不清楚。氯胺酮的（R）对映体，即开他敏，在暴露于 CRS 的小鼠中显示出快速抗抑郁样作用。
我们研究了开他敏是否可以改善暴露于 CRS 的小鼠大脑中的抑郁样行为和脱髓鞘。此外，我们还研究了转化生长因子β1（TGF-β1）在开他敏的有益作用中的作用。
单次给予开他敏（10mg/kg）可改善暴露于 CRS 的小鼠胼胝体中的抑郁样行为和脱髓鞘。在该区域发现了抑郁样行为与脱髓鞘之间的相关性。此外，TGF-β1 受体抑制剂 RepSox 的预处理显著阻断了开他敏对暴露于 CRS 的小鼠抑郁样行为和脱髓鞘的有益作用。最后，单次鼻腔给予 TGF-β1 可改善暴露于 CRS 的小鼠的抑郁样行为和脱髓鞘。
TGF-β1 参与开他敏作用的确切机制尚不清楚。
这些数据表明，胼胝体中 CRS 诱导的脱髓鞘可能导致抑郁样行为，而开他敏可以通过 TGF-β1 依赖的机制减轻这些变化。
