Evidence of hydrogen sulfide involvement in amyotrophic lateral sclerosis.

Alessandro Davoli, Viviana Greco, Alida Spalloni, Ezia Guatteo, Cristina Neri, Giada Ricciardo Rizzo, Alberto Cordella, Andrea Romigi, Claudio Cortese, Sergio Bernardini, Paola Sarchielli, Gabriela Cardaioli, Paolo Calabresi, Nicola B Mercuri, Andrea Urbani, Patrizia Longone

Index: Ann. Neurol. 77(4) , 697-709, (2015)

Full Text: HTML

Abstract

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.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.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.This study unravels H2 S as an astroglial mediator of motor neuron damage possibly involved in the cellular death characterizing ALS.© 2015 American Neurological Association.