Impact of Pharmacological Inhibition of Hydrogen Sulphide Production in the SOD1G93A-ALS Mouse Model
2019
Alida Spalloni | Viviana Greco | Giulia Ciriminna | Victor Corasolla Carregari | Federica Marini | Luisa Pieroni | Nicola B. Mercuri | Andrea Urbani | Patrizia Longone
A number of factors can trigger amyotrophic lateral sclerosis (ALS), although its precise pathogenesis is still uncertain. In a previous study done by us, poisonous liquoral levels of hydrogen sulphide (H<sub>2</sub>S) in sporadic ALS patients were reported. In the same study very high concentrations of H<sub>2</sub>S in the cerebral tissues of the familial ALS (fALS) model of the SOD1G93A mouse, were measured. The objective of this study was to test whether decreasing the levels of H<sub>2</sub>S in the fALS mouse could be beneficial. Amino-oxyacetic acid (AOA)—a systemic dual inhibitor of cystathionine-β-synthase and cystathionine-γ lyase (two key enzymes in the production of H<sub>2</sub>S)—was administered to fALS mice. AOA treatment decreased the content of H<sub>2</sub>S in the cerebral tissues, and the lifespan of female mice increased by approximately ten days, while disease progression in male mice was not affected. The histological evaluation of the spinal cord of the females revealed a significant increase in GFAP positivity and a significant decrease in IBA1 positivity. In conclusion, the results of the study indicate that, in the animal model, the inhibition of H<sub>2</sub>S production is more effective in females. The findings reinforce the need to adequately consider sex as a relevant factor in ALS.
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