Therapeutic potentials of neural stem cells treated with fluoxetine in Alzheimer’s disease

Recent studies have proposed that chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. However, the effect of antidepressants on fetal neural stem cells (NSCs) has not been well defined.Our study shows the dose-dependent effects of fluoxetine on the proliferation and neural differentiation of NSCs. Fluoxetine, even at nanomolar concentrations, stimulated proliferation of NSCs and increased the number of βIII-tubulin (Tuj 1)- and neural nucleus marker (NeuN)-positive cells, but not glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that fluoxetine can enhance neuronal differentiation. In addition, fluoxetine has protective effects against cell death induced by oligomeric amyloid beta (Aβ42) peptides.Taken together, these results clearly show that fluoxetine promotes both the proliferation and neuronal differentiation of NSCs and exerts protective effects against Aβ42-induced cytotoxicities in NSCs, which suggest that the use of fluoxetine is applicable for cell therapy for various neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases by its actions in NSCs.

► Fluoxetine increased the proliferation of neural stem cells.
► Fluoxetine increased the neuronal differentiation of neural stem cells.
► Fluoxetine protected neural stem cells against oligomeric Aβ.