Glial D-serine modulates oligodendrocyte lineage progression under inflammatory conditions
Year: 2026
Type: article
Abstract: Inflammatory environments may shape oligodendrocyte lineage dynamics beyond classical cytokine signaling, in part through the release of glial neuromodulators. Here, we investigated whether inflammation-associated D-serine signaling modulates oligodendrocyte lineage progression. Using highly purified primary oligodendrocyte precursor cell (OPC) cultures, we show that D-serine exposure during late differentiation reduces the proportion of OLIG2 + and myelin basic protein–positive (MBP + ) cells without altering net cell number, while selectively decreasing apoptosis within the mature MBP + population. These findings indicate that D-serine attenuates late-stage lineage progression while preserving oligodendrocyte survival in vitro . In parallel, inflammatory activation of mixed glial cultures with lipopolysaccharide (LPS) increased tumor necrosis factor- α release, upregulated serine racemase expression, and elevated extracellular D-serine levels. Conditioned media from reactive glial cultures recapitulated the effects of D-serine on OPC maturation, which were prevented by enzymatic degradation of D-serine or pharmacological blockade of N-methyl-D-aspartate receptors (NMDARs). Together, these findings support the involvement of glia-derived D-serine as a modulatory signal influencing oligodendrocyte lineage progression consistent with NMDAR-dependent mechanisms under inflammatory conditions that may contribute to impaired remyelination.
Institutions: Universidad Bernardo O'Higgins, University of Chile
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7136165355