Abstract
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.
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Acknowledgements
The authors would like to thank Dr. Rocío González-Vieira from UAM-I for animal supply and Dr. Ruth Rincón Heredia from IFC-UNAM and the CBS-UAMI Confocal Core for confocal images acquisition and analysis. Dr. Anahí Chavarría for her guidance in the cytokines field. This work was supported by CONACyT grant FON.INST/298/2016, as well as the “Red Temática de Investigación en Salud y Desarrollo Social” from CONACYT. Maciel-Barón, Silva-Palacios and Morales-Rosales are CONACyT scholarship holders.
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Maciel-Barón, L.Á., Morales-Rosales, S.L., Silva-Palacios, A. et al. 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. Biogerontology 19, 415–433 (2018). https://doi.org/10.1007/s10522-018-9767-3
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DOI: https://doi.org/10.1007/s10522-018-9767-3