Objectives <p>This study investigated the effects of the H<sub>2</sub>S donor sodium hydrosulfide (NaHS) on demyelination and behavioral deficits in a cuprizone (CPZ)-induced experimental rat model of MS.</p> Methods <p>The rats were fed chow pellets supplemented with 1% CPZ for 5&#xa0;weeks, and NaHS (50 and 100&#xa0;μmol/kg) was administered during the last 2&#xa0;weeks. For behavioral assessment, grip strength, passive avoidance, rota rod and elevated plus maze tests were performed. Nuclear factor kappa-B (NF-κB) and interleukin-1 beta (IL-1β) were measured to assess inflammation in brain tissue. Demyelination in the corpus callosum (CC) was assessed by immunohistochemistry for myelin basic protein (MBP), platelet-derived growth factor receptor α (PDGFRα) and Glial fibrillary acidic protein (GFAP). The TUNEL method was used to assess apoptosis.</p> Results <p>Demyelination in the CC was reduced in the NaHS-treated groups. NaHS increased the amount of MBP and decreased the amount of PDGFRα and GFAP immunoreactive cells. NaHS reduced NF-κB, IL-1β levels, and the number of apoptotic cells in the brain tissue. In addition, NaHS improved muscle strength, motor coordination, learning and memory, and showed a significant anxiolytic effect. However, it was found that the beneficial effects of NaHS decreased at a high dose of 100&#xa0;μmol/kg.</p> Conclusion <p>H<sub>2</sub>S showed neuroprotective effects by reducing demyelination, inflammation and apoptosis in the CPZ-induced MS model. H<sub>2</sub>S also improved muscle strength, motor coordination, learning and memory and showed anxiolytic activity. Anti-inflammatory, anti-apoptotic and antioxidant effects may play a role in the neuroprotective effects of H<sub>2</sub>S.</p>

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Hydrogen Sulfide Alleviates Demyelination, Behavioral and Motor Impairments in a Cuprizone-Induced Rat Model of Multiple Sclerosis

  • Yasemin Tekşen,
  • Fikriye Yasemin Özatik,
  • Orhan Özatik

摘要

Objectives

This study investigated the effects of the H2S donor sodium hydrosulfide (NaHS) on demyelination and behavioral deficits in a cuprizone (CPZ)-induced experimental rat model of MS.

Methods

The rats were fed chow pellets supplemented with 1% CPZ for 5 weeks, and NaHS (50 and 100 μmol/kg) was administered during the last 2 weeks. For behavioral assessment, grip strength, passive avoidance, rota rod and elevated plus maze tests were performed. Nuclear factor kappa-B (NF-κB) and interleukin-1 beta (IL-1β) were measured to assess inflammation in brain tissue. Demyelination in the corpus callosum (CC) was assessed by immunohistochemistry for myelin basic protein (MBP), platelet-derived growth factor receptor α (PDGFRα) and Glial fibrillary acidic protein (GFAP). The TUNEL method was used to assess apoptosis.

Results

Demyelination in the CC was reduced in the NaHS-treated groups. NaHS increased the amount of MBP and decreased the amount of PDGFRα and GFAP immunoreactive cells. NaHS reduced NF-κB, IL-1β levels, and the number of apoptotic cells in the brain tissue. In addition, NaHS improved muscle strength, motor coordination, learning and memory, and showed a significant anxiolytic effect. However, it was found that the beneficial effects of NaHS decreased at a high dose of 100 μmol/kg.

Conclusion

H2S showed neuroprotective effects by reducing demyelination, inflammation and apoptosis in the CPZ-induced MS model. H2S also improved muscle strength, motor coordination, learning and memory and showed anxiolytic activity. Anti-inflammatory, anti-apoptotic and antioxidant effects may play a role in the neuroprotective effects of H2S.