Impact of Pharmacological Inhibition of Hydrogen Sulphide Production in the SOD1G93A-ALS Mouse Model

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 (H2S) in sporadic ALS patients were reported. In the same study very high concentrations of
H2S 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 H2S in the fALS mouse could
be beneficial. Amino-oxyacetic acid (AOA)—a systemic dual inhibitor of cystathionine--synthase
and cystathionine-
lyase (two key enzymes in the production of H2S)—was administered to fALS
mice. AOA treatment decreased the content of H2S in the cerebral tissues, and the lifespan of female
mice increased by approximately ten days, while disease progression in male mice was not aected.
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 H2S production is more eective in females. The findings
reinforce the need to adequately consider sex as a relevant factor in ALS