The plastic d-serine signaling pathway: Sliding from neurons to glia and vice-versa

Abstract

d-Serine is now recognized as the main co-agonist for NMDA receptors. For years it was thought to be exclusively produced by astrocytes and was thus viewed as the archetype of gliotransmitters. Recent research have challenged this long cherished and appealing view by showing that in physiological conditions d-erine would rather originate from neurons but not from glia. In the present review and in the light of the emerging serine shuttle model, we ambition to offer a new reading direction of the glia-neuron cross-talk in shaping the metabolism and the functions of d-serine in cerebral communication in normal and pathological conditions by re-interpretating some seminal findings.

Keywords: Gliotransmission; N-methyl d-aspartate receptors; Serine racemase; Serine shuttle; d-Amino acid oxidase; d-Serine.