Roles of metabotropic glutamate receptors in glial function and glial-neuronal communication

Winder, Danny G.; Conn, P. Jeffrey

doi:10.1002/(sici)1097-4547(19961015)46:2<131::aid-jnr1>3.0.co;2-i

Cited by 68 publications

(43 citation statements)

References 46 publications

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“…mGluR1a is also expressed in glial processes in the monkey STN , and the monkey and rat SNr . A growing body of evidence suggests that group I mGluRs expressed in glial cells are involved in intracellular signaling and glial function (e. g., Ca 2+ mobilization and regulation of K + conductance; for a review see Winder and Conn, 1996). Group II and Group III mGluRs-In contrast to the extensive information currently available for group I mGluRs in the basal ganglia, little is known about the subsynaptic localization of group II and group III mGluRs.…”

Section: Glial Expression Of Group I Mglursmentioning

confidence: 99%

Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

2006

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GABA and glutamate, the main transmitters in the basal ganglia, exert their effects through ionotropic and metabotropic receptors. The dynamic activation of these receptors in response to released neurotransmitter depends, among other factors, on their precise localization in relation to corresponding synapses. The use of high resolution quantitative electron microscope immunocytochemical techniques has provided in-depth description of the subcellular and subsynaptic localization of these receptors in the CNS. In this article, we review recent findings on the ultrastructural localization of GABA and glutamate receptors and transporters in the basal ganglia, at synaptic, extrasynaptic and presynaptic sites. The anatomical evidence supports numerous potential locations for receptor-neurotransmitter interactions, and raises important questions regarding mechanisms of activation and function of synaptic versus extrasynaptic receptors in the basal ganglia.

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Section: Glial Expression Of Group I Mglursmentioning

confidence: 99%

Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

2006

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“…Glutamate-induced Ca 2ϩ elevation is also believed to promote excitotoxic neuronal cell death associated with brain injury and disease (15). Recently, particular attention has been paid to the role of mGluRs in regulating glial cell functions such as proliferation, glutamate uptake, and modulation of neuronal activity (10,35,38). mGluR5 is one of the most abundant and best-characterized glutamate receptors in glial cells.…”

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confidence: 99%

Essential Role for Epidermal Growth Factor Receptor in Glutamate Receptor Signaling to NF-κB

Sitcheran

Comb

Cogswell

et al. 2008

Molecular and Cellular Biology

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Glutamate is a critical neurotransmitter of the central nervous system (CNS) and also an important regulator of cell survival and proliferation. The binding of glutamate to metabotropic glutamate receptors induces signal transduction cascades that lead to gene-specific transcription. The transcription factor NF-B, which regulates cell proliferation and survival, is activated by glutamate; however, the glutamate receptorinduced signaling pathways that lead to this activation are not clearly defined. Here we investigate the glutamate-induced activation of NF-B in glial cells of the CNS, including primary astrocytes. We show that glutamate induces phosphorylation, nuclear accumulation, DNA binding, and transcriptional activation function of glial p65. The glutamate-induced activation of NF-B requires calcium-dependent IB kinase ␣ (IKK␣) and IKK␤ activation and induces p65-IB␣ dissociation in the absence of IB␣ phosphorylation or degradation. Moreover, glutamate-induced IKK preferentially targets the phosphorylation of p65 but not IB␣. Finally, we show that the ability of glutamate to activate NF-B requires cross-coupled signaling with the epidermal growth factor receptor. Our results provide insight into a glutamate-induced regulatory pathway distinct from that described for cytokine-induced NF-B activation and have important implications with regard to both normal glial cell physiology and pathogenesis.

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“…Activation of mGluR3 in astrocytes stimulates the production and release of neurotrophic factors, including transforming growth factor-β (TGF-β), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) (Bruno et al 1998;Ciccarelli et al 1999;Battaglia et al 2009;Di Liberto et al 2010), which is involved in mGluR3-mediated neuroprotective activity (Bruno et al 1998;Corti et al 2007;Durand et al 2008). The above observations favor a concept that the mGluR3-mediated neuronal effect involves an intimate crosstalk between neurons and glial cells (Winder and Conn 1996;Bruno et al 1997). mGluR3 also participates in gliogenesis, as activation of mGluR3 favors the undifferentiated state and prevents astroglial differentiation (Ciccarelli et al 1997;Ciceroni et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor 3 Is Downregulated and Its Expression Is Shifted From Neurons to Astrocytes in the Mouse Lateral Septum During the Postpartum Period

Zhao

Gammie

2015

J Histochem Cytochem.

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Summary The inhibitory metabotropic glutamate receptor 3 (mGluR3) plays diverse and complex roles in brain function, including synaptic plasticity and neurotransmission. We recently found that mGluR3 is downregulated in the lateral septum (LS) of postpartum females using microarray and qPCR analysis. In this study, we used double fluorescence immunohistochemical approaches to characterize mGluR3 changes in LS of the postpartum brain. The number of mGluR3-immunoractive cells was significantly reduced in the dorsal (LSD) and intermediate (LSI) but not ventral (LSV) parts of the LS in postpartum versus virgin females. mGluR3 immunoreactivity in the LS was found predominantly in neurons (~70%), with a smaller portion (~20%–30%) in astrocytes. Colocalization analysis revealed a reduced mGluR3 expression in neurons but an increased astrocytic localization in postpartum LSI. This change in the pattern of expression suggests that mGluR3 expression is shifted from neurons to astrocytes in postpartum LS, and the decrease in mGluR3 is neuron-specific. Because mGluR3 is inhibitory and negatively regulates glutamate and GABA release, decreases in neuronal expression would increase glutamate and GABA signaling. Given our recent finding that ~90% of LS neurons are GABAergic, the present data suggest that decreases in mGluR3 are a mechanism for elevated GABA in LS in the postpartum state.

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Roles of metabotropic glutamate receptors in glial function and glial-neuronal communication

Cited by 68 publications

References 46 publications

Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

Essential Role for Epidermal Growth Factor Receptor in Glutamate Receptor Signaling to NF-κB

Metabotropic Glutamate Receptor 3 Is Downregulated and Its Expression Is Shifted From Neurons to Astrocytes in the Mouse Lateral Septum During the Postpartum Period

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