Methane-Rich Saline Ameliorates Depressive-Like Behaviors During Chronic Unpredictable Mild Stress (CUMS)

Abstract

Depression is considered the most prevalent neuropsychiatric disorder, which is also a multifactorial and complex disease. Oxidative stress and inflammation are essential contributors to the occurrence and progression of depression. On the other hand, methane is a new therapeutic gas that has been effective in increasing tissue resistance against ischemic injuries and inflammation, so this study was conducted to investigate the effect of methane-rich saline (MRS) on depression. The chronic unpredictable mild stress (CUMS) model was designed with daily mild stressors for two months. MRS was used to treat depressed rats. Depression-like behaviors were assessed with sucrose preference, open field, and forced swimming tests. Besides, the cognitive performance of the animals was determined by the Morris water maze. Serum corticosterone levels, the activity of antioxidant enzymes, and hippocampal malondialdehyde (MDA) levels were measured, and histological changes in the hippocampus were also investigated. The results indicated that MRS decreased depressive-like behaviors and cognitive impairment in depressed animals by increasing the ratio of sucrose consumption, elevating exploratory behaviors in the open field test, reducing immobility in the forced swimming test, and improving memory and learning in the Morris water maze. Additionally, the administration of MRS regulated the corticosterone level in the serum. The level of hippocampal lipid peroxidation and tissue damage was also reduced in treated animals. The results of the present study show that MRS reduces tissue damage and lipid peroxidation in the hippocampus of CUMS animals, which is followed by a significant improvement in behavioral and cognitive functions. Probably, MRS affects by reducing oxidative stress and improving the hypothalamus-pituitary-adrenal axis function.