Metabotropic glutamate receptor-mediated signaling in neuroglia

Abstract

Metabotropic glutamate (mGlu) receptors are G-protein-coupled receptors, including eight subtypes classified into three groups (I-III) based upon sequence homology, signal transduction mechanism and pharmacological profile. Although most studied with regard to neuronal function and modulation, mGlu receptors are also expressed by neuroglia-including astrocytes, microglia, and oligodendrocytes. Activation of mGlu receptors on neuroglia under both physiologic and pathophysiologic conditions mediates numerous actions that are essential for intrinsic glial cell function, as well as for glial-neuronal interactions. Astrocyte mGlu receptors play important physiological roles in regulating neurotransmission and maintaining neuronal homeostasis. However, mGlu receptors on astrocytes and microglia also serve to modulate cell death and neurological function in a variety of pathophysiological conditions such as acute and chronic neurodegenerative disorders. The latter effects are complex and bidirectional, depending on which mGlu receptor subtypes are activated. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.