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.
Lamas
Mónica
M
Departamento de Farmacobiología, CINVESTAV Sede Sur, Calzada de los Tenorios 235, México, D.F., Mexico. mlamas@cinvestav.mx
Lee-Rivera
Irene
I
Ramírez
Mónica
M
López-Colomé
Ana María
AM
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012694:Serine / Q000378:metabolism* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D012694:Serine