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. INTERPRETATION:This study unravels H2 S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Davoli A,Greco V,Spalloni A,Guatteo E,Neri C,Rizzo GR,Cordella A,Romigi A,Cortese C,Bernardini S,Sarchielli P,Cardaioli G,Calabresi P,Mercuri NB,Urbani A,Longone P

doi

10.1002/ana.24372

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

697-709

issue

4

eissn

0364-5134

issn

1531-8249

journal_volume

77

pub_type

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