Disturbance of hippocampal H<sub>2</sub>S generation contributes to CUMS-induced depression-like behavior: involvement in endoplasmic reticulum stress of hippocampus

Abstract

The chronic unpredictable mild stress (CUMS) model is a widely used experimental model of depression. Exogenous stress-induced neuronal cell death in the hippocampus is closely associated with the pathogenesis of depression. Excessive and prolonged endoplasmic reticulum (ER) stress triggers cell death. Hydrogen sulfide (H2S), the third endogenous signaling gasotransmitter, plays an important role in brain functions as a neuromodulator and a neuroprotectant. We hypothesized that the disturbance of endogenous H2S generation and ER stress in the hippocampus might be involved in CUMS-induced depression-like behaviors. Thus, the present study focused on whether CUMS disturbs the generation of endogenous H2S and up-regulates ER stress in the hippocampus and whether exogenous H2S prevents CUMS-induced depressive-like behaviors. Results showed that CUMS-treated rats exhibit depression-like behavior and hippocampal ER stress responses including up-regulated levels of glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein, and cleaved caspase-12 expression, while the endogenous generation of H2S in the hippocampus is suppressed in CUMS-treated rats. Furthermore, exogenous H2S prevents CUMS-induced depression-like behavior. These data indicated that CUMS-induced depression-like behaviors are related to the disturbance of endogenous H2S generation and ER stress in the hippocampus and suggested that endogenous H2S and ER stress are novel treatment targets of depression.

Nelumbo nucifera Gaertn Stems (Hegeng) Improved Depression Behavior in CUMS Mice by Regulating NCAM and GAP‐43 Expression

“…We used the CUMS protocol to mimic the traits of depression, which were confirmed by the SPT, FST, TST, EPM, and OFT in mice in our behavioral studies. FLU is currently available on the market [35], and the present results are consistent with previous research [36]. e CUMS mouse model has been generally used to study the pathological mechanism of depressive disorder and screening antidepressant drugs [37].…”

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

“…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].…”

Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress‐Induced Oxidative Stress in Hippocampus by Upregulation of BDNF‐TrkB Pathway

“…In addition, recent report demonstrated that exogenous H 2 S alleviated the oxidative stress-induced rat hippocampal damage through its antioxidant effects [ 17 ]. Moreover, we have previously provided compelling evidence that CUMS induced the imbalance of proportion to endogenous H 2 S in hippocampus [ 18 ]. Thus, we speculated that H 2 S attenuates oxidative stress in hippocampus of CUMS-treated rats.…”