Protective Effect Of Hydrogen Sulfide On Chronic Stress-induced Neural Injury In Hippocampus

[Background and objective]Chronic stress caused the disorder in hypothalamic-pituitary-adrenocortical (HPA) system, the excessive release of excitatory amino acids (EAAs), resulting in oxidative stress and apoptosis of hippocampal neurons, ultimately caused depreesion or anxiety. How to protect the hippocampus from injury caused by chronic stress is significant to therapy for the patients. Hydrogen sulfide (H2S), a gas signaling molecule and a novel neuromodulator, has important roles in neuroregulation and neuroprotection. Therefore, this work will establish the model of Chronic Unpredictable Mild Stress (CUMS) to explore the protection of hydrogen sulfide against chronic stress-induced damage of hippocampus.[METHODS]1. The rats were divided into four groups, including control, CUMS, model+low concentration NaHS (1.68mg/kg), model+high concentration NaHS (5.6mg/kg), then treated with chronic unpredictable mild stress (CUMS) except.the control group.2. After treatment with chronic mild stress, the generation of H2S in hippocampus was determined by methylene blue methed;3. Arrangement and morphology of hippocampal neuron was observed by HE staining.4. Apoptosis of hippocampal neuron was measured by Tunel assay.5. The expression of Klotho was determined by ELISA.6. The neurogensis in hippocampus was detected by Brdu staining.[RESULTS]1. After chronic unpredictable mild stress four weeks, the arrangement and morphology of hippocampal neuron was observed by HE staining. In comparison with control group, the arrangement of hippocampal neuron is deranged, the shape of neuron is abnormal, and the loss of hippocampal neurons is increase in CA3in the CUMS group. Howerver, treatment with NaHS ameliorates these changes, which suggests that H2S protects hippocampal neuron against chronic stress-induced damage.2. After chronic unpredictable mild stress four weeks, apoptosis of hippocampal neuron was measured by Tunel assay. The results showed that the amount of apoptotic hippocampal neuron in CUMS group was significantly increased; however, NaHS was significantly prevented CUMS-induced apoptosis in hippocampus. The data suggest that H2S protects hippocampal neuron against chronic stress-induced apoptosis.3. The expression of Kloth protein in hippocampus was significantly down-regulated by CUMS. However, NaHS reversed this effect of CUMS.4. The generation of H2S in hippocampal tissue was makedly reduced by CUMS; however, treatment with NaHS significantly attenuated the reduced H2S generation in hippocampal tissue by CUMS.5. The neurogensis of hippocampus was determined by the Brdu immunohistochemical. CUMS markedly inhibited the neurogensis in hippocampus but treatment with NaHS significantly prevented CUMS-caused inhibition in hippocampus neurogensis. [CONCLUSIONS]Hydrogen sulfide plays an important role in resisting chronic stress-induced hippocampus damagment by reversing chronic stress-induced down regulation of Klotho, decrease in H2S generation, and inhibition of hippocampus neurogensis.