Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress.

The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal development and organization. The modulation of microtubule dynamics depends on the phosphorylation of neuronal microtubule-associated proteins (MAPs). Chronic unpredicted mild stress (CUMS) affects hippocampal structure and function in the rat. The aim of the present work was to investigate the possible alteration of cytoskeleton in the hippocampus of rats exposed to CUMS and re-exposed to CUMS to mimic depression and the recurrence of depression of human. We investigated the effects of CUMS, fluoxetine and re-exposure to CUMS on alpha-tubulin isoforms associated with microtubule dynamics, MAP-2 and phospho-MAP-2 in the hippocampus of rats. Our results showed that rats submitted to CUMS once showed a significant reduction in locomotion and sucrose preference which indicate a state of anhedonia. These behavioral alterations were accompanied by specific alterations in hippocampal alpha-tubulin isoforms and phospho-MAP-2 expression, indicating less microtubule dynamics and the possible mechanism. Treatment of fluoxetine could reverse CUMS-induced impairment. Moreover, there were more dramatically changes in behaviors, alpha-tubulin isoforms and phospho-MAP-2 of rats re-exposed to CUMS compared to the rats exposed to CUMS once. These findings provide evidence that rats exposed to CUMS and re-exposed to CUMS showed impairment of microtubule dynamics accompanied with the decreased level of phospho-MAP-2, providing insight into the role of cytoskeleton in the depression and recurrent of depression.