Effects of Continuous Moderate Intensity Training and Fluoxetine on Neuroplasticity Biomarkers in the Brain of Wistar Rats with Depression

<ns4:p>Background Depression is a complex psychiatric disorder that requires a multimodal approach for effective treatment. This study aimed to explore the influence of moderate-intensity continuous exercise, fluoxetine administration, and the combination effects on serum corticosterone concentrations and the gene expression of neuroplasticity markers within the prefrontal cortex. This study specifically examined the gene expression of spermidine synthase, vesicular glutamate transporter-1 (V-GluT1), metabolotropic glutamate receptor-1 (m-GluR1), and fibroblast growth factor-2 (FGF-2) in male Wistar rats with depression. Methods Twenty-five male Wistar rats aged 12 weeks were randomly allocated into five distinct groups (n = 5/group): Negative Control Group (NCG), Positive Control Group (PCG), PCG with medical intervention (PCG + FLX; fluoxetine 10 mg/kg/day), PCG with physical activity intervention (PCG + MCT; moderate-intensity treadmill running at 15 m/min for 30 min/day), and PCG with combined interventions (PCG + FLX + MCT). Depression was induced by chronic isolation and unpredictable mild stress for 8 weeks. Serum corticosterone levels were measured at baseline, week 4, and week 8. The gene expression of spermidine synthase, V-GluT1, M-GluR1, and FGF-2 in the prefrontal cortex was quantified at week 8 using real-time PCR. Results Chronic social isolation with unpredictable mild stress induced a 12.5-fold increase in serum corticosterone levels in the PCG group compared with the NCG group by week 8 (36091.87 vs. 23602.12 ng/mL; p &lt; 0.05). All interventions decreased corticosterone levels. Gene expression analysis revealed that the intervention correlated with increased expression of the neurotrophic factors FGF-2 (p &lt; 0.05) and Spermidine Synthase(p &lt; 0.05), V-GluT1 (p &lt; 0.05), and m-GluR1 (p &lt; 0.05). Conclusion The combination of moderate-intensity exercise and fluoxetine therapy showed a synergistic effect, enhancing the restoration of neuroplasticity biomarkers beyond the capabilities of either treatment alone. These findings advocate the integration of physical activity with antidepressant medication as a comprehensive approach to depression management.</ns4:p>