Chronic exercise reduces astrocytic c-Fos and CCL2 via conditioned serum and cerebrospinal fluid.

Inflammation, a critical immune response to infection and tissue damage, is mediated by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which upregulate the expression of cellular proto-oncogene Fos (c-Fos) and chemokine ligand 2 (CCL2). Chronic exercise has been shown to exert systemic anti-inflammatory effects, yet its impact on astrocytic inflammatory signaling remains unclear. The aim of this study was to investigate whether chronic exercise modulates astrocytic expression of c-Fos and CCL2 through factors present in conditioned serum and cerebrospinal fluid (CSF). Male wistar rats were assigned to an exercise group (progressively increased swimming, five times per week for four weeks) or a sedentary control group. Conditioned serum and CSF were collected and applied to astrocyte cultures with or without TNF-α induction. After 120 minutes, c-Fos and CCL2 expression were quantified using western blot analysis. Conditioned serum and CSF from exercise rats significantly reduced TNF-α induced c-Fos and CCL2 expression compared with controls. These findings suggest that chronic exercise may attenuate neuroinflammatory responses by modulating astrocytic expression of c-Fos and CCL2. The parallel reductions observed in both serum and CSF indicate that exercise-induced circulating factors may possess anti-inflammatory properties within neural environments. This study provides preliminary in vitro evidence for mechanistic link between chronic exercise and reduced neuroinflammation, underscoring the need for in vivo validation and translational research to assess therapeutic potential.