Effect of alpha-lipoic acid on the depressive-like behavior in oophorectomized rats: Neuroprotective actions of apelin and microRNA 99a

Abstract

Background: Postmenopausal sharp decline in estrogen levels leads to significant mood and cognitive changes. Although estrogen replacement therapy can alleviate these symptoms, it is not suitable for all women. Alpha-lipoic acid (ALA) is a naturally occurring compound with reported antidepressant effects. Apelin, an adipokine, exerts neuroprotective actions, while microRNA-99a (miRNA-99a) has emerged as a depression-related regulator.Objectives: assessing ALA's potential antidepressant effects in oophorectomized female rats, focusing on its effect on apelin and miRNA-99a expression in the brain.Materials and methods: Thirty-two female rats were divided into four groups (control, oophorectomized, estradiol-treated, and ALA-treated). Depressive-like behavior was assessed using behavioral tests. Neurotransmitters, Nrf2, apelin, inflammatory and oxidative stress markers were measured by ELISA and colorimetric assays. MiRNA-99a expression was quantified using real-time PCR.Results: In oophorectomized group, IL-6 and NF-κB increased significantly, while other biochemical and molecular markers decreased compared with controls (p<0.001). ALA and estradiol significantly improved behavioral outcomes, biochemical and molecular parameters, with ALA producing more significant effects. IL-6 decreased to 45.0±5.29 and 57.25±4.89 pg/mg, and NF-κB to 7.7±1.1 and 5.38±0.92 ng/mg, respectively (p<0.001). Dopamine and serotonin increased with ALA (15.0±1.77 and 15.13±1.46 ng/mg) and estradiol (18.5±1.2 and 19.63±1.51 ng/mg) (p<0.001). ALA induced higher Nrf2 (172.5±9.24 vs 121.5±6.55 pg/mg), apelin (242.1±11.7 vs 204.8±15.3 pg/mg), CAT (5.8±0.83 vs 3.56±0.5 U/g), GPx (32.88±4.52 vs 23.13±2.1 U/g), and miRNA-99a (0.68±0.04 vs 0.50±0.07 fold change) (all p<0.001).Conclusion: These results refer to the promising role of ALA in postmenopausal depression that is augmented by its linking with apelin and miRNA-99a expression.