G protein-coupled receptor signalling in astrocytes in health and disease: A focus on metabotropic glutamate receptors

Department of Cell Physiology and Pharmacology, College of Medicine, Biological Science & Psychology, University of Leicester, University Road, Leicester, LE1 9HN, United Kingdom.
Biochemical pharmacology (Impact Factor: 5.01). 04/2012; 84(3):249-59. DOI: 10.1016/j.bcp.2012.04.009
Source: PubMed


Work published over the past 10-15 years has caused the neuroscience community to engage in a process of constant re-evaluation of the roles of glial cells in the mammalian central nervous system. Recent emerging evidence suggests that, in addition to carrying out various homeostatic functions within the CNS, astrocytes can also engage in a two-way dialogue with neurons. Astrocytes possess many of the receptors, and some of the ion channels, present in neurons endowing them with an ability to sense and respond to an array of neuronal signals. In addition, an expanding number of small molecules and proteins have been shown to be released by astrocytes in both health and disease. In this commentary we will highlight advances in our understanding of G protein-coupled receptor signalling in astrocytes, with a particular emphasis on metabotropic glutamate (mGlu) receptors. Discussion will focus on the major mGlu receptors expressed in astrocytes, mGlu3 and mGlu5, how these receptors can influence different aspects of astrocyte physiology, and how signalling by these G protein-coupled receptors might change under pathophysiological circumstances.

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    • "Astrocytes are also involved control of neurotransmitter uptake from the extracellular space during neurotransmission, thereby regulating neurotransmitter concentrations in the synaptic cleft and the strength and duration of synaptic communication. In the case of the modulation of excitatory neurotransmitter release, although some synaptically released glutamate can be taken up by presynaptic or postsynaptic neuronal transporters or diffuses away from the synapse, the vast majority of glutamate uptake is carried out by astrocytic Na + -dependent glutamate transporters [194]. A recent study demonstrates that activation of astrocytic G q -coupled group I mGluRs by a tetanic high-frequency stimulus [195] in hippocampal slices results in astrocytic glutamate uptake [196]. "
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    • "Group I includes mGluR1 and mGluR5 subtypes, which are coupled to phosphoinositide hydrolysis [3] [4]. mGluR5 is expressed in both neurons and astrocytes and plays an important role in the regulation of the glio-neuronal cross-talk under both physiological and pathological conditions [5] [6] [7] [8]. Moreover, several lines of evidence indicate that mGluR5 is involved in early developmental processes, including proliferation, differentiation , and survival of neural progenitors ([9] [10] [11]; for review see [12]). "
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