| Autor: |
De Stefano S; Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.; Laboratory of Molecular Neurobiology, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Tiberi M; Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.; Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Salvatori I; Laboratory of Neurochemistry, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., De Bardi M; Neuroimmunology Unit, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Gimenez J; Laboratory of Molecular Neurobiology, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Pirshayan M; Laboratory of Molecular Neurobiology, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Greco V; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.; Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, 00168 Rome, Italy., Borsellino G; Neuroimmunology Unit, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Ferri A; Laboratory of Neurochemistry, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.; Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy., Valle C; Laboratory of Neurochemistry, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.; Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy., Mercuri NB; Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.; Laboratory of Experimental Neurology, Santa Lucia Foundation IRCCS, 00143 Rome, Italy., Chiurchiù V; Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.; Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy., Spalloni A; Laboratory of Molecular Neurobiology, IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Longone P; Laboratory of Molecular Neurobiology, IRCCS Santa Lucia Foundation, 00143 Rome, Italy. |
| Abstrakt: |
Hydrogen sulfide (H 2 S), a known inhibitor of the electron transport chain, is endogenously produced in the periphery as well as in the central nervous system, where is mainly generated by glial cells. It affects, as a cellular signaling molecule, many different biochemical processes. In the central nervous system, depending on its concentration, it can be protective or damaging to neurons. In the study, we have demonstrated, in a primary mouse spinal cord cultures, that it is particularly harmful to motor neurons, is produced by glial cells, and is stimulated by inflammation. However, its role on glial cells, especially astrocytes, is still under-investigated. The present study was designed to evaluate the impact of H 2 S on astrocytes and their phenotypic heterogeneity, together with the functionality and homeostasis of mitochondria in primary spinal cord cultures. We found that H 2 S modulates astrocytes' morphological changes and their phenotypic transformation, exerts toxic properties by decreasing ATP production and the mitochondrial respiration rate, disturbs mitochondrial depolarization, and alters the energetic metabolism. These results further support the hypothesis that H 2 S is a toxic mediator, mainly released by astrocytes, possibly acting as an autocrine factor toward astrocytes, and probably involved in the non-cell autonomous mechanisms leading to motor neuron death. |
