title: Evidence of hydrogen sulfide involvement in amyotrophic lateral sclerosis.
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.
  
  
  CONCLUSIONS
  This study unravels H2 S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS.
authors: Neurophysiopathology Unit.
authors: Alessandro
authors: A
authors: Davoli
authors: Viviana
authors: V
authors: Greco
authors: Alida
authors: A
authors: Spalloni
authors: Ezia
authors: E
authors: Guatteo
authors: Cristina
authors: C
authors: Neri
authors: Giada Ricciardo
authors: GR
authors: Rizzo
authors: Alberto
authors: A
authors: Cordella
authors: Andrea
authors: A
authors: Romigi
authors: Claudio
authors: C
authors: Cortese
authors: Sergio
authors: S
authors: Bernardini
authors: Paola
authors: P
authors: Sarchielli
authors: Gabriela
authors: G
authors: Cardaioli
authors: Paolo
authors: P
authors: Calabresi
authors: Nicola B
authors: NB
authors: Mercuri
authors: Andrea
authors: A
authors: Urbani
authors: Patrizia
authors: P
authors: Longone
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000134:cerebrospinal fluid*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006862:Hydrogen Sulfide