Traditional pediatric massage exerted an antidepressant effect and activated IGF-1/Nrf2 pathway in CUMS-exposed adolescent rats

The activation of insulin-like growth factor-1 (IGF-1)/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway contributes to enhance anti-inflammatory M2 microglia polarization and inhibit proinflammatory M1 microglia polarization, which is essential to resist neuroinflammation and thus resist depression. The prevalence of depression is high in adolescents, who are hypersensitive to chronic stress. Traditional pediatric massage (TPM) can effectively relieve depression. In this study, we investigated the action mechanism of TPM on preventing depression-like behaviors in adolescent rats exposed to chronic unpredictable mild stress (CUMS). In this investigation, we employed several behavioral tests and detections, including western blotting, immunofluorescence staining and RT-qPCR. The findings of this study demonstrated that TPM had an effectively antidepressant effect, maintained microglia polarization homeostasis and resisted neuroinflammation in the hippocampus in CUMS-exposed adolescent rats. With the treatment of picropodophyllin, the inhibitor of IGF-1 receptor, the antidepressant effect of TPM was blocked, along with inhibited IGF-1/Nrf2 pathway which were closely related with anti-inflammatory and anti-ferroptosis actions. The results suggest that TPM enhanced the resilience of adolescent rats to CUMS and exerted an antidepressant effect partially via activating IGF-1/Nrf2 pathway.