Functional glutamate signaling in neural progenitor cells

摘要

In this review, we have summarized our recent studies on the functionality of ionotropic (iGluR) and metabotropic (mGluR) glutamate receptors expressed by undifferentiated neural progenitor cells (NPC) isolated from embryonic rat and mouse brains. NPC are primitive cells with the self-renewal capacity as well as the multipotentiality to generate different neural lineages including neurons, astrocytes, and oligodendrocytes. Isolated cells were cultured in the presence of growth factors for the formation of round spheres by clustered cells so-called 'neurospheres' under floating conditions. Reverse transcription polymerase chain reaction analyses revealed expression of mRNA for particular iGluR and mGluR subtypes in NPC. Moreover, sustained exposure to an agonist for the N-methyl-D-aspartate receptor (NMDAR) not only inhibited the formation of neurospheres but also promoted differentiation of NPC into cells immunoreactive to a neuronal marker protein on immunocytochemistry and western blot analyses. On the other hand, sustained exposure to an agonist for the group III mGluR subtype led to suppression of proliferation activity in these neurospheres along with facilitation of the subsequent differentiation into astrocytes. Accordingly, glutamate could play a pivotal role in the mechanisms underlying proliferation for self-replication, together with determination of the subsequent differentiation fate toward particular progeny lineages through activation of NMDAR and group III mGluR subtypes in NPC. © 2011 The Pharmaceutical Society of Japan.