Le Thi-Hung, Li Ling, Rami Fatima Zahra, Oh Jung-Mi, Chun Sungkun, Chung Young-Chul
Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Korea.
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.
Clin Psychopharmacol Neurosci. 2025 Feb 28;23(1):110-119. doi: 10.9758/cpn.24.1212. Epub 2024 Oct 21.
Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer's disease, Parkinson's disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS).
We measured protein expression levels of α-tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS.
We observed lower levels of acetylated α-tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated α-tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group. Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group.
Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions. These findings underscore the complexity of EpoD's effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.
埃坡霉素D（EpoD）作为一种微管（MT）稳定剂，在阿尔茨海默病、帕金森病和精神分裂症的动物模型中显示出有前景的结果。本研究旨在探讨EpoD对社会挫败应激（SDS）诱导的MT相关蛋白和内质网（ER）应激蛋白变化的预防作用。
我们测量了用EpoD（2mg/kg）或其溶剂二甲基亚砜（DMSO）处理并暴露于SDS的C57BL/6J品系小鼠前额叶皮质（PFC）和海马体（HIP）中α-微管蛋白及其翻译后修饰、微管相关蛋白2、1和2及其磷酸化形式，以及ER应激标志物78-kDa葡萄糖调节蛋白（GRP-78）和CCAAT/增强子结合蛋白（C/EBP）-同源蛋白（CHOP）的蛋白表达水平。
与DMSO-Con组相比，我们观察到EpoD-Con组PFC中乙酰化α-微管蛋白、MAP2、p-STMN（Ser16）和GRP-78水平较低。另一方面，在HIP中，与DMSO-Defeat组相比，EpoD-Defeat组酪氨酸化α-微管蛋白和GRP-78水平显著更高。此外，与DMSO-Con组相比，发现EpoD-Con组HIP中MAP2水平较低。
我们的结果表明，EpoD表现出双重影响，根据脑区不同，对SDS诱导的MT相关蛋白和ER应激蛋白的异常变化既有有益作用也有有害作用。这些发现强调了EpoD作用的复杂性，需要进一步探索以了解其在与SDS相关的细胞途径中的复杂机制。
