The secretory phenotype of senescent astrocytes isolated from Wistar newborn rats changes with anti-inflammatory drugs, but does not have a short-term effect on neuronal mitochondrial potential

• Published in: Biogerontology (Dordrecht) 2018-10, Vol.19 (5), p.415-433
• Main Authors: Maciel-Barón, Luis Ángel, Morales-Rosales, Sandra Lizbeth, Silva-Palacios, Alejandro, Rodríguez-Barrera, Roxana Haydee, García-Álvarez, Jorge Antonio, Luna-López, Armando, Pérez, Viviana Isabel, Torres, Claudio, Königsberg, Mina
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Astrocytes; Astrocytes - drug effects; Astrocytes - immunology; Biomedical and Life Sciences; Cell Biology; Cellular Senescence - drug effects; Cellular Senescence - immunology; Central nervous system; Central Nervous System - drug effects; Central Nervous System - immunology; Central Nervous System - metabolism; Chemokines; Dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; Developmental Biology; Epithelial cells; Fibroblasts; Geriatrics/Gerontology; Inflammation; Interleukin 10; Interleukin 6; Interleukin-1alpha - immunology; Isothiocyanates - pharmacology; Life Sciences; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Models, Animal; Neurodegeneration; Neurons - drug effects; Neurons - metabolism; Oxidative stress; Oxidative Stress - physiology; Phenotypes; Proteasomes; Rats; Rats, Wistar; Research Article; Rodents; Senescence; Sulforaphane
• ISSN: 1389-5729; 1573-6768
• DOI: 10.1007/s10522-018-9767-3

In the central nervous system (CNS), senescent astrocytes have been associated with neurodegeneration. Senescent cells secrete a complex mixture of pro-inflammatory factors, which are collectively called Senescence Associated Secretory Phenotype (SASP). The SASP components can vary depending on the cell type, senescence inducer and time. The SASP has been mainly studied in fibroblasts and epithelial cells, but little is known in the context of the CNS. Here, the SASP profile in senescent astrocytes isolated from Wistar newborn rats induced to senescence by oxidative stress or by proteasome inhibition was analyzed. Senescent astrocytes secreted predominantly chemokines and IL-1α, but no IL-6. The effect of the anti-inflammatory drugs, sulforaphane (SFN) and dehydroepiandrosterone (DHEA), on the SASP profile was evaluated. Our results showed that SFN and DHEA decreased IL-1α secretion while increasing IL-10, thus modifying the SASP to a less anti-inflammatory profile. Primary neurons were subjected to the conditioned media obtained from drug-treated senescent astrocytes, and their mitochondrial membrane potential was evaluated.