Fluoxetine increases hippocampal neural survival by improving axonal transport in stress-induced model of depression male rats.

INTRODUCTION

Axonal transport deficit is a key mechanism involved in neurodegenerative conditions. Fluoxetine, a commonly used antidepressant for treatment of depression, is known to regulate several important structural and neurochemical aspects of hippocampal functions. However, the mechanisms underlying these effects are still poorly understood. This study aimed to investigate the effects of chronic fluoxetine treatment on axonal transport in the hippocampus of rat stress-induced model of depression.

METHODS

We have analyzed the effects of chronic fluoxetine treatment (20 mg/kg/day, 24 days) on immobility behavior (forced swimming test), hippocampal iNOS (inflammatory factor) expression (RT-PCR) as well as hippocampal BDNF, kinesin and dynein expression (RT-PCR) and hippocampal neuronal survival (Nissl staining).

RESULTS

This study provided evidence that fluoxetine could effectively suppress iNOS expression following unpredictable chronic mild stress (P < 0.01), increase hippocampal BDNF (P < 0.01), kinesin (P < 0.05) and dynein (P < 0.01) gene expression, and control neuronal death in CA1 (P < 0.01) and CA3 regions (P < 0.01) of the hippocampus and thereby improve immobility behavior (P < 0.001).

CONCLUSION

Based on the findings of this study, we concluded the neuroprotective effect of fluoxetine may be due to its ability to improve axonal transmission, followed by increased energy supply and neurotrophin concentration and function.