Evidence of hydrogen sulfide involvement in amyotrophic lateral sclerosis. Issue 4 (13th March 2015)

• Record Type: Journal Article
• Authors: Davoli, Alessandro; Greco, Viviana; Spalloni, Alida; Guatteo, Ezia; Neri, Cristina; Rizzo, Giada Ricciardo; Cordella, Alberto; Romigi, Andrea; Cortese, Claudio; Bernardini, Sergio; Sarchielli, Paola; Cardaioli, Gabriela; Calabresi, Paolo; Mercuri, Nicola B.; Urbani, Andrea; Longone, Patrizia
• Is Part Of: Annals of neurology. Volume 77:Issue 4(2015:Apr.)
• Page Start: 697
• Page End: 709
• Publication Date: 2015-03-13
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24372
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : Objective: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease whose pathophysiological deficits, causing impairment in motor function, are largely unknown. Here we propose that hydrogen sulfide (H2 S), as a glial‐released inflammatory factor, contributes to ALS‐mediated motor neuron death. Methods: H2 S concentrations were analyzed in the cerebrospinal fluid of 37 sporadic ALS patients and 14 age‐ and gender‐matched controls, in tissues of a familial ALS (fALS) mouse model, and in spinal cord culture media by means of a specific and innovative high‐performance liquid chromatography method. The effects of H2 S on motor neurons cultures was analyzed immunohistochemically and by patch clamp recordings and microfluorometry. Results: We found a significantly high level of H2 S in the spinal fluid of the ALS patients. Consistently, we found increased levels of H2 S in the tissues and in the media from mice spinal cord cultures bearing the fALS mutation SOD1G93A. In addition, NaHS, an H2 S donor, added to spinal culture, obtained from control C57BL/6J mice, is toxic for motor neurons, and induces an intracellular Ca 2+ increase, attenuated by the intracytoplasmatic application of adenosine triphosphate. We further show that H2 S is mainly released by astrocytes and microglia. Interpretation: This study unravels H2 S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS. Ann Neurol 2015;77:697–709