IGF-1 defends against chronic-stress induced depression in rat models of chronic unpredictable mild stress through the PI3K/Akt/FoxO3a pathway

Abstract

This study aims to investigate the role of IGF-1 in chronic-stress induced depression through the PI3K/Akt/FoxO3a pathway. A rat model of chronic unpredictable mild stress (CUMS) was established. In total, 48 rats were randomized into control (normal rats), CUMS (CUMS modeled rats) and CUMS + IGF-1 (injection of IGF-1 before CUMS modeling) groups. Body weight, horizontal (number of horizontal crossing) and vertical activity (rearing times), and sucrose consumption were identified one day before and after the open-field test. The mRNA and protein expression of PI3K, Akt, FoxO3a and Bim in the hippocampus was measured by RT-qPCR and Western blotting, respectively. Compared with the control group, a lower body weight, a decreased number of horizontal crossings, reduced rearing times and lower sucrose consumption were observed in the CUMS and CUMS + IGF-1 groups after the test. However, a higher body weight, number of horizontal crossings, rearing times and sucrose consumption were found in the CUMS + IGF-1 group than those in the CUMS group. Compared with the control group, mRNA and protein expression of PI3K, Akt and FoxO3a was decreased, and Bim mRNA and protein expression was increased in the CUMS + IGF-1 and CUMS groups. Meanwhile, in comparison to the CUMS group, mRNA and protein expression of PI3K, Akt and FoxO3a was elevated, and Bim mRNA and protein expression was reduced in the CUMS + IGF-1 group. The results suggested that IGF-1 exerted an antidepressant-like effect on chronic-stress induced depression through the PI3K/Akt/FoxO3a pathway. Keywords: IGF-1, Chronic-stress induced depression, Rat models, Chronic unpredictable mild stress, PI3K/Akt/FoxO3a signaling pathway