Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway

Abstract

Aim: Homocysteine (Hcy) can elicit neuronal cell death, and hyperhomocysteinemia is a strong independent risk factor for Alzheimer's disease. The aim of this study was to examine the effects of hydrogen sulfide (H 2 S) on Hcy-induced endoplasmic reticulum (ER) stress and neuronal apoptosis in rat hippocampus. Methods: Adult male SD rats were intracerebroventricularly (icv) injected with Hcy (0.6 μmol/d) for 7 d. Before Hcy injection, the rats were treated with NaHS (30 or 100 μmol·kg -1 ·d -1 , ip) and/or k252a (1 μg/d, icv) for 2 d. The apoptotic neurons were detected in hippocampal coronal slices with TUNEL staining. The expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, and BDNF in the hippocampus were examined using Western blotting assays. The generation of H 2 S in the hippocampus was measured with the NNDPD method. Results: Hcy markedly inhibited the production of endogenous H 2 S and increased apoptotic neurons in the hippocampus. Furthermore, Hcy induced ER stress responses in the hippocampus, as indicated by the upregulation of GRP78, CHOP, and cleaved caspase-12. Treatment with the H 2 S donor NaHS increased the endogenous H 2 S production and BDNF expression in a dosedependent manner, and significantly reduced Hcy-induced neuronal apoptosis and ER stress responses in the hippocampus. Treatment with k252a, a specific inhibitor of TrkB (the receptor of BDNF), abolished the protective effects of NaHS against Hcy-induced ER stress in the hippocampus. Conclusion: H 2 S attenuates ER stress and neuronal apoptosis in the hippocampus of Hcy-treated rats via upregulating the BDNF-TrkB pathway.

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

“…A previous study from Wang et al [68] has revealed that BDNF/TrkB signaling pathway might mediate the neuroprotective effect of curcumin against glutamate excitotoxicity. Moreover, our recent studies have demonstrated that up-regulation of the BDNF-TrkB pathway is responsible for the H 2 S-exerted inhibitory effect on homocysteineinduced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus [67] and that BDNF-TrkB pathway is involved in the H 2 S-induced neuroprotective effect against the neurotoxicity of formaldehyde [57]. According to these observations, we think that up-regulation of BDNF-TrkB is sufficient and necessary for neuronal protection.…”

“…BDNF is a member of the neurotrophin family and the activity of BDNF is mediated by the high-affinity TrkB receptor [64]. Accumulated observations have demonstrated that BDNF induces neuroprotective effects [65][66][67]. Therefore, we focused on the role of BDNF in the protective effect of H 2 S against the corticosterone-induced neurotoxicity.…”

The Effect of Hippocampal Cognitive Impairment and XIAP on Glucose and Lipids Metabolism in Rats

“…Hippocampal neuron apoptosis is the main pathological change of many cognitive disorders, such as AD [7,8]. Cysteinyl aspartate specific proteinase (caspase) plays a critical role in apoptosis and mediates apoptosis through many pathways [9][10][11].…”

Xiao Yao San against Corticosterone-Induced Stress Injury via Upregulating Glucocorticoid Receptor Reaction Element Transcriptional Activity

“…The inhibition of BDNF-TrkB signaling pathway is associated with memory impairment in corticosterone treatment animals [35]. Caveolin-1 is localised to the growth cones and dendrites of hippocampal neurons and it promotes neuronal differentiation and maturation [36].…”