Antidepressant-like and anxiolytic-like effects of hydrogen sulfide in streptozotocin-induced diabetic rats through inhibition of hippocampal oxidative stress

Abstract

Depression is highly prevalent in individuals with diabetes, and depressive symptoms are less responsive to current antidepressant therapies. Oxidative stress plays a major role both in the pathogenesis of diabetes and in major depression and anxiety disorders. Hydrogen sulfide (H2S), the third gaseous mediator, is a novel signaling molecule in the brain that has both antioxidative activity and antidepressant-like and anxiolytic-like effects. We hypothesized that H2S could produce antidepressant-like and anxiolytic-like effects in diabetic patients through its antioxidative effect. To test this hypothesis, we generated streptozotocin (STZ)-induced diabetic rats. We found that H2S alleviated depressive-like behaviors of STZ-induced diabetic rats in the forced swimming and tail suspension tests and reduced their anxiety-like behaviors in the elevated plus maze test. We also found that H2S significantly reduced levels of malondialdehyde and 4-hydroxynonenal and elevated levels of superoxide dismutase and reduced glutathione in the hippocampus of STZ-induced diabetic rats. The results provide evidence for antidepressant-like and anxiolytic-like effects of H2S in STZ-induced diabetic rats and suggest that the therapeutic effects may result from inhibition of hippocampal oxidative stress. These findings suggest that elevating H2S signaling is a potential target for treatment of depressive and anxiety disorders related to diabetes.

Chronic Administration of Rosa canina Hydro-Alcoholic Extract Attenuates Depressive-Like Behavior and Recognition Memory Impairment in Diabetic Mice: A Possible Role of Oxidative Stress

“…Further, the diabetes modelling in mice using STZ increased lipid peroxidation, decreased TAC, and disturbed oxidative stress steady state in the mouse brain, similar to previous studies [5,9] in which it was reported that diabetes induction using STZ increased lipid peroxidation and decreased Color version available online TAC in the rodent brain. A probable explanation could be that insulin signaling systems are turned off in a diabetic state, leading to distortion of glucose metabolism and changes in mitochondrial energy production, reduced ATP production, and increased reactive oxygen species in the brain as reported previously [20] .…”

“…The depressive-like behavior has been observed in diabetic animals using different behavioral tasks such as tail suspension and forced swimming tests [8,9] . Also, evidence has shown that inhibition of hippocampal oxidative stress can exert antidepressant-like effects on diabetic animal models [9] .…”

“…Also, evidence has shown that inhibition of hippocampal oxidative stress can exert antidepressant-like effects on diabetic animal models [9] . The recognition memory impairment had been reported using different cognitional tasks such as novel object recognition (NOR) or placement tests in rodent models of diabetes [10,11] .…”

H<sub>2</sub>S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway

“…It was reported that the neurotoxicity of corticosterone plays an important role in the development of depression [14,15]. In addition, our recent studies have shown that H 2 S has antidepressant-like effect [25,26]. Thus, we suggest that the anti-depressive effect of H 2 S may be related to its inhibitory effect against the corticosterone-induced neurotoxicity…”

“…A recent report has documented that the endogenous H 2 S level is decreased in chronic unpredictable mild stress (CUMS) [24]. In addition, our recent studies showed that H 2 S could prevent depressive-like actions in the behavioral models of depression [25,26]. These data imply that H 2 S may be a potential therapeutic target for the treatment of depression.…”