Long-term fluoxetine administration induces changes in microtubule plasticity mediated by CRMP2 in differentiated PC12 cells

Abstract Backgroud Depression is a neuropsychiatric disease with a high risk of relapse. Clinical guidelines advocate whole course of antidepressant treatment, but the relapse rate of MDD is still high. Methods We intended to study the changes in microtubule scaffold plasticity induced by long-term antidepressant administration in PC12 cell to explore the possible mechanism of depression relapse. Results The cell activity of NC group decreased after 3 days of culture. The results of immunofluorescence showed the extension of processes was obvious on the first day in Flu group and NC group, but neurite connections were inhibited on the third day in Flu group.CRMP2 and Tubulin were co-located by IF, and Co-IP confirmed the interaction between CRMP2 and Tubulin. RT-PCR showed the mRNA expression of CRMP2 and Tubulin increased on the first and second day in Flu group, but decreased on the third day. Similarly, Western Blotting showed the contents of CRMP2 and Tubulin protein in Flu group increased on the first day, but decreased on the third day. The expression of CRMP2 and Tubulin was affected by changes in the activity of CRMP2. Conclusions The long-term fluoxetine administration can affect the microtubule scaffold plasticity in PC12 cell, and CRMP2 is involved in this process. This may be one of the biological bases of the high risk for depression relapse induced by long-term antidepressant administration.