The protective effect of fluoxetine on hippocampal oligodendrocytes in AD mice: a potential mechanism involving S100B

Abstract

Fluoxetine (FLX) plays a crucial role in delaying the progression of Alzheimer's disease (AD) and opens up new avenues for investigating the mechanisms of AD. Previous research has shown that FLX has a protective effect on oligodendrocytes in the hippocampus of transgenic AD mice. However,the mechanism underlying this effect remains unclear. In this study, we treated 8-month-old APP/PS1 transgenic mice with FLX for 10 weeks and examined the behavioral changes, the levels of S100B protein, the numbers of hippocampus oligodendrocytes and the co-localization of S100B in oligodendrocytes and astrocytes in the hippocampus. Furthermore, we analyzed the damaging effects of exogenous S100B on an oligodendrocyte cell line in vitro and investigated whether fluoxetine could reverse these damages. Our findings demonstrate that FLX delays the decline of hippocampus-dependent spacial learning and memory abilities and the loss of hippocampal oligodendrocytes in AD mice. We also observed a positive correlation between the total number of hippocampal oligodendrocytes and the hippocampal volume. Additionally, FLX reduces hippocampal S100B levels and the expression of S100B in both astrocytes and oligodendrocyte progenitor cells in AD mice. Our cell-based experiments indicate that FLX prevents S100B-induced impairments in oligodendrocyte differentiation and maturation. Moreover, the protective effect of FLX may be associated with the preservation of mitochondrial autophagy and the upregulation of transcription and differentiation factors. Overall, our results highlight the potential mechanisms underlying the protective effect of fluoxetine on S100B-induced impairment of oligodendrocyte differentiation and maturation in AD, and propose a new target for the prevention and treatment of AD.