Effects of Epothilone D on Social Defeat Stress-induced Changes in Microtubule-related and Endoplasmic Reticulum...

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.