d-Serine regulates CREB phosphorylation induced by NMDA receptor activation in Müller glia from the retina

d-Serine is an N-methyl-d-aspartate (NMDA) receptor coagonist predominantly produced by glial cells in the brain and the retina. Whereas a role for d-serine as a modulator of NMDA receptors in neurons has been suggested, its function in glial cells has not been analyzed. We here show that d-serine modulates gene expression in Müller glial cells from the retina through the induction of transcription factor CREB phosphorylation and the expression of the immediate-early gene c-fos. Pharmacological analysis indicates that d-serine effect involves NMDA receptor activation. Comparison of the effect of d-serine in Müller cells, hippocampal astrocytes and hippocampal neurons suggests that d-serine could function as a retinal NMDA receptor coagonist activating functionally relevant transcription factor pathways in glial cells.