TY - JOUR
T1 - Evidence of Hydrogen Sulfide Involvement in Amyotrophic Lateral
Sclerosis
AU - Davoli, Alessandro
AU - Greco, Viviana
AU - Spalloni, Alida
AU - Guatteo, Ezia
AU - Neri, Cristina
AU - Rizzo, Giada Ricciardo
AU - Cordella, Alberto
AU - Romigi, Andrea
AU - Cortese, Claudio
AU - Bernardini, Sergio
AU - Sarchielli, Paola
AU - Cardaioli, Gabriela
AU - Calabresi, Paolo
AU - Mercuri, Nicola B
AU - Urbani, Andrea
AU - Longone, Patrizia
PY - 2015
Y1 - 2015
N2 - OBJECTIVE: \r\n\r\nAmyotrophic 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.\r\n\r\nMETHODS: \r\n\r\nH2 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.\r\n\r\nRESULTS: \r\n\r\nWe 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.\r\n\r\nINTERPRETATION: \r\n\r\nThis study unravels H2 S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS.
AB - OBJECTIVE: \r\n\r\nAmyotrophic 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.\r\n\r\nMETHODS: \r\n\r\nH2 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.\r\n\r\nRESULTS: \r\n\r\nWe 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.\r\n\r\nINTERPRETATION: \r\n\r\nThis study unravels H2 S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS.
KW - Proteomics
KW - Proteomics
UR - https://publicatt.unicatt.it/handle/10807/79804
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84925632087&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84925632087&origin=inward
U2 - 10.1002/ana.24372
DO - 10.1002/ana.24372
M3 - Article
SN - 0364-5134
VL - 77
SP - 697
EP - 709
JO - Annals of Neurology
JF - Annals of Neurology
IS - 4
ER -