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Exogenous hydrogen sulfide ameliorates diabetes-associated cognitive dysfunction by regulating the nrf-2/HO-1 axis
Huinan Chen1, Hongxue Sun1, Wei Hua2
1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Abstract:
Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus that leads to an increased risk of cognitive impairment and dementia. However, the molecular mechanism underlying DACD has not been elucidated, and a promising therapy for this disease remains to be established. Hydrogen sulfide (H2S), a significant antioxidative and anti-inflammatory gasotransmitter, has emerged as a neuroprotective agent. In this study, we investigated the protective effects of H2S on DACD in a streptozotocin (STZ)-induced diabetic rat model. We applied the Morris water maze to evaluate spatial learning and memory abilities. We used Western blotting and immunohistochemical staining to investigate the expression of the Nrf-2/HO-1 axis and the NLRP3 inflammasome. After NaHS (H2S donor) administration, diabetic rats exhibited improved spatial learning and memory retrieval abilities in the Morris water maze. In STZ-induced diabetic rats, the protein expression levels of the Nrf-2/HO-1 axis, the NLRP3 inflammasome and subsequent inflammatory cytokines in the hippocampal region were elevated compared to those in control rats. Exogenous H2S triggered Nrf-2/HO-1 antioxidant activity and inhibited NLRP3 inflammasome activation and proinflammatory cytokine expression. These findings suggested that exogenous H2S has neuroprotective effects by modulating the Nrf-2/HO-1 axis and the NLRP3 inflammasome pathway, which were found to be associated with DACD. H2S treatment may be a promising therapeutic strategy for preventing the progression of tissue damage caused by DACD.
Insights
Hydrogen sulfide (H2S) protects against diabetes-associated cognitive dysfunction by reducing inflammation and oxidative stress. This study shows H2S therapy improves memory in diabetic rats, offering a promising treatment for cognitive decline.
Area of Science:
- Neuroscience
- Biochemistry
- Endocrinology
Background:
- Diabetes-associated cognitive dysfunction (DACD) is a growing concern linked to diabetes mellitus, increasing dementia risk.
- The precise molecular mechanisms driving DACD remain unclear, necessitating novel therapeutic strategies.
- Hydrogen sulfide (H2S), a gasotransmitter with antioxidant and anti-inflammatory properties, shows potential neuroprotective effects.
Purpose of the Study:
- To investigate the neuroprotective potential of exogenous hydrogen sulfide (H2S) in a rat model of diabetes-associated cognitive dysfunction (DACD).
- To elucidate the molecular pathways, specifically the Nrf-2/HO-1 axis and NLRP3 inflammasome, involved in H2S-mediated neuroprotection in DACD.
Main Methods:
- A streptozotocin (STZ)-induced diabetic rat model was utilized to mimic DACD.
- Spatial learning and memory were assessed using the Morris water maze.
- Western blotting and immunohistochemical staining were employed to analyze the expression of the Nrf-2/HO-1 axis, NLRP3 inflammasome, and inflammatory cytokines in the hippocampus.
Main Results:
- Administration of NaHS (an H2S donor) significantly improved spatial learning and memory in STZ-induced diabetic rats.
- Diabetic rats exhibited elevated levels of Nrf-2/HO-1 axis proteins, NLRP3 inflammasome, and inflammatory cytokines in the hippocampus.
- Exogenous H2S treatment normalized Nrf-2/HO-1 antioxidant activity and suppressed NLRP3 inflammasome activation and pro-inflammatory cytokine expression.
Conclusions:
- Exogenous H2S exerts neuroprotective effects in DACD by modulating the Nrf-2/HO-1 antioxidant pathway and inhibiting the NLRP3 inflammasome.
- These findings highlight the critical role of oxidative stress and inflammation in DACD pathogenesis.
- H2S treatment presents a promising therapeutic avenue for mitigating cognitive decline and tissue damage associated with diabetes.
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