De Stefano Susanna, Tiberi Marta, Salvatori Illari, De Bardi Marco, Gimenez Juliette, Pirshayan Mahsa, Greco Viviana, Borsellino Giovanna, Ferri Alberto, Valle Cristiana, Mercuri Nicola B, Chiurchiù Valerio, Spalloni Alida, Longone Patrizia
Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Laboratory of Molecular Neurobiology, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
Antioxidants (Basel). 2024 Oct 15;13(10):1241. doi: 10.3390/antiox13101241.
Hydrogen sulfide (HS), 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 HS on astrocytes and their phenotypic heterogeneity, together with the functionality and homeostasis of mitochondria in primary spinal cord cultures. We found that HS 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 HS 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.
硫化氢（HS）是一种已知的电子传递链抑制剂，在外周以及中枢神经系统中内源性产生，主要由神经胶质细胞生成。作为一种细胞信号分子，它影响许多不同的生化过程。在中枢神经系统中，根据其浓度不同，它对神经元可能具有保护作用或造成损害。在本研究中，我们在原代小鼠脊髓培养物中证实，它对运动神经元特别有害，由神经胶质细胞产生，并受到炎症刺激。然而，其对神经胶质细胞，尤其是星形胶质细胞的作用仍研究不足。本研究旨在评估HS对星形胶质细胞及其表型异质性的影响，以及原代脊髓培养物中线粒体的功能和稳态。我们发现，HS调节星形胶质细胞的形态变化及其表型转化，通过降低ATP生成和线粒体呼吸速率发挥毒性作用，扰乱线粒体去极化，并改变能量代谢。这些结果进一步支持了以下假设：HS是一种主要由星形胶质细胞释放的毒性介质，可能作为针对星形胶质细胞的自分泌因子起作用，并可能参与导致运动神经元死亡的非细胞自主机制。
