Palmitate-Induced Primary Rat Senescent Astrocytes Exhibit Higher Inflammatory Activity and a Distinct Transcriptomic Profile Compared to Reactive Astrocytes

Astrocytes play a crucial role in mediating neuroinflammation, particularly under pathological conditions where they can enter into senescent or gliotic states. This study explored the induction of these two astrocytic states using the same stressor, palmitate, in primary cortical astrocytes. A transcriptomic analysis revealed distinct expression profiles both astrocytes phenotypes. Senescent astrocytes upregulated genes involved in cell cycle arrest and the Senescence-Associated Secretory Phenotype (SASP), including IGFBP5, CDKN1A, and p53. In contrast, reactive astrocytes upregulated genes related to immune response, complement activation, and inflammation, such as C3, LCN2, and pro-inflammatory cytokines like IL-11 and CXCL12. Despite these differences, both astrocytic states shared pro-inflammatory characteristics, contributing to neuroinflammation. The secretory profiles further distinguished the two states: senescent astrocytes produced higher levels of interleukins, including IL-6 and IL-18, indicative of sustained inflammatory responses. Gliotic astrocytes, on the other hand, secreted higher levels of chemokines, such as MCP-1 and GRO-α, involved in immune cell recruitment and tissue repair. Senescent astrocytes were more active in cytokine production, while gliotic astrocytes promoted immune responses and tissue repair through chemokine production. Understanding these distinct roles provides valuable insights for developing therapeutic interventions to mitigate neuroinflammation and support healthy brain aging.