Targeting microglial dysfunction: The antioxidant potential of and the regulation of microglial responsiveness by dermatan sulfate from a marine invertebrate.

Microglia are the main immune cells of the central nervous system (CNS) and are responsible for maintaining tissue homeostasis. Their chronic activation contributes to neuroinflammation and the progression of neurodegenerative diseases (NDs). Dermatan sulfate (DS) obtained from the ascidian Phallusia nigra (PnDS) exhibits the same sulfation pattern (IdoUA(2S)-GalNAc(6S)) as DS found in neurogenic regions of adult mammals. In the present study, the effects of PnDS on the modulation of murine BV-2 microglial cells subjected to paraquat (PQ)-induced oxidative stress were investigated. Cells were divided into eight groups: control (I); PQ (II); dexamethasone (DEX) (III); mammalian heparin (MH) (IV); PnDS (V); and co-incubation groups DEX + PQ, MH + PQ, and PnDS+PQ (VI, VII, and VIII, respectively). Cell morphology, mitochondrial activity, reactive oxygen species (ROS) production, antioxidant enzymatic activity, and lipid peroxidation (LPO) were subsequently assessed. The results demonstrated that PQ exposure induced an amoeboid-like phenotype in BV-2 cells, associated with mitochondrial dysfunction and increased ROS production. Co-treatment with PQ and PnDS (0.025 μg/mL) significantly attenuated these alterations, restoring both cellular morphology and mitochondrial activity. Moreover, PnDS reduced ROS production and LPO levels more effectively than DEX and MH. Catalase (CAT) activity was significantly increased following PnDS treatment, whereas superoxide dismutase (SOD) activity remained unchanged. In conclusion, the biological effects of PnDS are associate with their structural features. Elucidation of the molecular mechanisms underlying these effects may contribute to the development of novel therapeutic strategies targeting neuroinflammatory processes associated with neurodegenerative disorders.