Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 2026 4 2026 06 21 63 70 Sahar Seddighi Department of Exercise Physiology, Ka. C., Islamic Azad University, Karaj, Iran. Foad Feizolahi Department of Exercise Physiology, Ka. C., Islamic Azad University, Karaj, Iran. Amir Sarshin Department of Exercise Physiology, Ka. C., Islamic Azad University, Karaj, Iran. Alireza Rahimi Department of Exercise Physiology, Ka. C., Islamic Azad University, Karaj, Iran. 2026 02 26 2026 05 18 Objectives: Sciatic nerve injury is a neurological disorder that leads to muscle wasting and sensory-motor dysfunction. This study aimed to investigate the effects of combined lithium and resistance training intervention on histological, behavioral and molecular indices in rats modeled with sciatic nerve injury. Methods: In this study, 25 rats were randomly divided into five groups: sham, model (sciatic nerve injury), model + lithium (10 mg/kg, intraperitoneally for 5 days), model + resistance training (6 weeks) and model + lithium + resistance training. Interventions began 24 hours after injury. At the end of the 6-week period, the soleus muscle tissue was examined for histopathology and muscle fiber diameter. The behavioral response of the animals was assessed by hot plate test and the expression levels of Wnt and β-catenin genes in the cerebrospinal fluid were assessed by Real-time PCR. Results: The findings showed that the model group had a significant decrease in muscle fiber diameter and a significant increase in reaction time in the hot plate test compared to the sham group. Also, the expression of Wnt and β-catenin genes in the model group increased significantly. In contrast, the treatment groups, especially the combination group (lithium + resistance training), showed a significant improvement in muscle fiber diameter, a decrease in reaction time in the behavioral test and a decrease in the expression of Wnt and β-catenin genes compared to the model group (p<0.05). Conclusion: The results of this study suggest that combined lithium and resistance training therapy can improve muscle tissue structure and reduce sensory-motor disorders caused by sciatic nerve injury by reducing Wnt/β-catenin pathway activity. This combined approach can be considered as a promising therapeutic strategy for managing complications caused by peripheral nerve injuries. https://abi.tums.ac.ir/index.php/abi/article/view/184 https://abi.tums.ac.ir/index.php/abi/article/download/184/139