Protective effects of hydrogen sulfide on chronic stress-induced hippocampal neural injury in rats and its mechanisms

Abstract

Objective To investigate the protective effect of hydrogen sulfide (H2S) on chronic unpredictable mild stress (CUMS)-induced damage in hippocampus of rats and explore potential mechanisms. Methods 40 SD rats were divided into four groups, including control, CUMS, CUMS co-treated with NaHS (1.68 mg/kg×14 d, ip) and CUMS co-treated with NaHS (5.6 mg/kg×14 d, ip) groups.After treatment with CUMS for 4 weeks, arrangement and morphology of hippocampal neuron were examined by HE staining, apoptosis of hippocampal neurons were measured by Tunel assay. Klotho expression was detected by ELISA. Meanwhile, the generation of H2S in the hippocampus was measured by spectrophotometry and the neurogenesis of hippocampus was detected by Brdu staining. Results The arrangement and morphology of CA3 hippocampal cells were disturbed and the neurogenesis in hippocampal DG region were inhibited in the CUMS group compared with control group.Moreover, the CUMS rats showed increased loss of hippocampal neurons(1.151±0.041, P<0.01), and the expression of klotho(0.910±0.032) and generation of H2S((0.445±0.025)nmol·mg-1·min-1) in CUMS rats were decreased in contrast to the control((0.621±0.019)nmol·mg-1·min-1, P<0.05). The sparse neuron and inhibited neurogenesis by CUMS in hippocampus of rats were improved by NaHS administration, and the loss of hippocampal neurons in CUMS + 1.68 mg/kg NaHS (1.032±0.023) or CUMS + 5.60 mg/kg NaHS(1.045±0.038) were decreased in contrast to the CUMS rats(P<0.01). Compared with CUMS group, the expression of klotho in CUMS + 1.68 mg/kg NaHS group(1.045±0.021)or CUMS + 5.6 mg/kg NaHS group(1.046±0.076) was up-regulated(P<0.05) and the generation of H2S in CUMS + 1.68 mg/kg NaHS group((0.582±0.008)nmol·mg-1·min-1)or CUMS + 5.6 mg/kg NaHS group((0.585±0.029)nmol·mg-1·min-1) was increased(all P<0.05). Conclusion H2S can antagonize the neural injury-induced by chronic stress probably by upregulating the expression of klotho protein, facilitating the production of H2S and promoting neurogenesis in hippocampus. Key words: Hydrogen sulfide; Chronic stress; Damage of hippocampus; Klotho; Neurogensis