Fluoxetine treatment for more than 2 days decreases the cellular neuroplasticity and microtubule plasticity in differentiated PC12 cells

Abstract

Background: Recent studies indicate that antidepressants treatment restores neuroplasticity. But some researchers claimed that antidepressants, including fluoxetine (FLU), may exacerbate neuroplasticity, which is contradictory and rarely studied. Since almost all of those studies treated with drugs for 1 to 2 days as treatment models of antidepressants, it is possible that FLU treatments for longer periods would have opposite effects on neuroplasticity. Results: In the present study, we examined the effects of FLU treatment up to 3 days on the cellular neuroplasticity and microtubule plasticity in PC12 cells. The cell viability of cells happened a small decease at 2 days (93.5±3.5%), followed by highly significant decreases at 3 days (71.4±4.4%). As report previously, cellular neuroplasticity was significantly upregulated with FLU treatment at 1 day, but that was inhibited FLU treatment at 3 days. Similarly, the expression of tubulin, which is microtubulin plasticity marker, was also upregulated with FLU treatment at 1 day. But it decreased significantly in cells treated with FLU at 3 days. Furthermore, we found tubulin interacted with CRMP2, which accelerated to cellular neuroplasticity, and the regulation of CRMP2 activity influenced microtubule plasticity. Conclusions: The results demonstrate that cellular neuroplasticity and microtubule plasticity were increased with FLU treatment at 1 day, but treatment with FLU for more than 2 days has opposite effect on them. The reduction in cellular neuroplasticity andmicrotubule plasticity with FLU treatment for more than 2 days might be involved in some aspects of the drugs’ therapeutic effects on depression.