{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:22:56Z","timestamp":1789982576888,"version":"4.0.1"},"reference-count":75,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:00:00Z","timestamp":1426204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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 (H<jats:sub>2<\/jats:sub>S), as a glial\u2010released inflammatory factor, contributes to ALS\u2010mediated motor neuron death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>H<jats:sub>2<\/jats:sub>S concentrations were analyzed in the cerebrospinal fluid of 37 sporadic ALS patients and 14 age\u2010 and gender\u2010matched controls, in tissues of a familial ALS (fALS) mouse model, and in spinal cord culture media by means of a specific and innovative high\u2010performance liquid chromatography method. The effects of H<jats:sub>2<\/jats:sub>S on motor neurons cultures was analyzed immunohistochemically and by patch clamp recordings and microfluorometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a significantly high level of H<jats:sub>2<\/jats:sub>S in the spinal fluid of the ALS patients. Consistently, we found increased levels of H<jats:sub>2<\/jats:sub>S in the tissues and in the media from mice spinal cord cultures bearing the fALS mutation SOD1G93A. In addition, NaHS, an H<jats:sub>2<\/jats:sub>S donor, added to spinal culture, obtained from control C57BL\/6J mice, is toxic for motor neurons, and induces an intracellular Ca<jats:sup>2+<\/jats:sup> increase, attenuated by the intracytoplasmatic application of adenosine triphosphate. We further show that H<jats:sub>2<\/jats:sub>S is mainly released by astrocytes and microglia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This study unravels H<jats:sub>2<\/jats:sub>S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS. 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