Abstract
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 (H2 S) in sporadic ALS patients were reported. In the same study very high concentrations of H2 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 H2 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 H2 S)—was administered to fALS mice. AOA treatment decreased the content of H2 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 H2 S production is more effective in females. The findings reinforce the need to adequately consider sex as a relevant factor in ALS.
| Original language | English |
|---|---|
| Article number | 2550 |
| Journal | International Journal of Molecular Sciences |
| Volume | 20 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - May 2 2019 |
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Keywords
- Amino-oxyacetic acid (AOA)
- Amyotrophic lateral sclerosis
- Glial cells
- Hydrogen sulphide
- Inflammation
- Pharmacology
ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
Cite this
Impact of pharmacological inhibition of hydrogen sulphide production in the SOD1G93A-ALS mouse model. / Spalloni, Alida; Greco, Viviana; Ciriminna, Giulia; Carregari, Victor Corasolla; Marini, Federica; Pieroni, Luisa; Mercuri, Nicola B.; Urbani, Andrea; Longone, Patrizia.
In: International Journal of Molecular Sciences, Vol. 20, No. 10, 2550, 02.05.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Impact of pharmacological inhibition of hydrogen sulphide production in the SOD1G93A-ALS mouse model
AU - Spalloni, Alida
AU - Greco, Viviana
AU - Ciriminna, Giulia
AU - Carregari, Victor Corasolla
AU - Marini, Federica
AU - Pieroni, Luisa
AU - Mercuri, Nicola B.
AU - Urbani, Andrea
AU - Longone, Patrizia
PY - 2019/5/2
Y1 - 2019/5/2
N2 - 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 (H2 S) in sporadic ALS patients were reported. In the same study very high concentrations of H2 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 H2 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 H2 S)—was administered to fALS mice. AOA treatment decreased the content of H2 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 H2 S production is more effective in females. The findings reinforce the need to adequately consider sex as a relevant factor in ALS.
AB - 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 (H2 S) in sporadic ALS patients were reported. In the same study very high concentrations of H2 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 H2 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 H2 S)—was administered to fALS mice. AOA treatment decreased the content of H2 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 H2 S production is more effective in females. The findings reinforce the need to adequately consider sex as a relevant factor in ALS.
KW - Amino-oxyacetic acid (AOA)
KW - Amyotrophic lateral sclerosis
KW - Glial cells
KW - Hydrogen sulphide
KW - Inflammation
KW - Pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85067281709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067281709&partnerID=8YFLogxK
U2 - 10.3390/ijms20102550
DO - 10.3390/ijms20102550
M3 - Article
C2 - 31137614
AN - SCOPUS:85067281709
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 10
M1 - 2550
ER -