Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and -5 on astrocyte proliferation in culture

Ciccarelli, Renata; Sureda, Francesc X.; Casabona, G.; Iorio, Patrizia Di; Caruso, Alessandra; Spinella, Francesca; Condorelli, D. F.; Nicoletti, Ferdinando; Caciagli, Francesco

doi:10.1002/(sici)1098-1136(199712)21:4<390::aid-glia6>3.0.co;2-7

Cited by 92 publications

(83 citation statements)

References 39 publications

(42 reference statements)

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“…This process may involve the release of calcium from intracellular stores and the generation of intercellular calcium waves, as shown in cultured astrocytes challenged with glutamate. [33][34][35] This 'synchronizing' activity of mGlu5 receptors might contribute to explain the heterogenous response of NPC cultures to MPEP or high concentrations of LY341495, as revealed by a distribution pattern of neurosphere diameters with multiple peaks (see Figure 5). Activation of mGlu5 receptors could also support NPC proliferation by stimulating the MAPK pathway, similarly to that observed for muscarinic 36,37 or opioid 38 receptor activation.…”

Section: Discussionmentioning

confidence: 98%

Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

et al. 2005

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The use of neural progenitor cells (NPCs) is limited by the incomplete knowledge of the extracellular signals regulating their proliferation and survival. We report that cultured mouse NPCs express functional mGlu3 and mGlu5 metabotropic glutamate receptors. Pharmacological blockade of both receptors reduced NPC proliferation and survival, whereas activation of mGlu5 receptors substantially enhanced cell proliferation. Adult mice lacking mGlu5 receptors or treated with mGlu5 or mGlu3 receptor antagonists showed a dramatic reduction in the number of dividing neuroprogenitors present in the subventricular zone and in the dentate gyrus of the hippocampus. These data disclose a novel function of mGlu receptors and offer new potential strategies for the optimization of cell replacement therapy in neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 98%

Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

et al. 2005

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“…The activation of mGluR2/3 have been implicated in the production of other neurotrophic factors, such as TGFb1 in astrocytes (Bruno et al, 1998;Ciccarelli et al, 1997) and in the striatum (D'Onofrio et al, 2001), or BDNF in microglia (Matarredona et al, 2001;Venero et al, 2002), in the hippocampus (Di Liberto et al, 2010), in neuronal hippocampal cultures (Canossa et al, 2001;Wu et al, 2004;Marini et al, 1998) and in reactive astrocytes (Mudo et al, 2007;Ohishi et al, 1993Ohishi et al, , 1998. Although this proved involvement of mGluR2/3 in neurotrophic factors regulation, the present data, together with previous related findings (Battaglia et al, 2009), provide a complete demonstration for an involvement of GDNF/RET neurotrophic system in the neuroprotection observed in the mouse model of Parkinson's disease following mGluR2/3 activation.…”

Section: Discussionmentioning

confidence: 99%

mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Erk1/2 in mouse striatum

Liberto¹,

Mudò²,

Belluardo³

2011

Neuropharmacology

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Keywords:GDNF RET mGluR2/3 LY379268 Erk1/2 TrK phosphorylation a b s t r a c tIn the present study we aimed to verify if the enhancement of glial cell line-derived neurotrophic factor (GDNF) production in mouse striatum following treatment with LY379268 may also induce in the nigrostriatal system a time-related activation of RET receptor and its specific intracellular signaling. For this purpose, we have investigated the effects of LY379268 treatment on RET phosphorylation at the Tyr1062 and on downstream signaling Erk1/2, Akt and PLCg1 pathway activation. The results showed that treatment with LY379268 (3 mg/kg) induces a significant increase of GDNF levels and time-related RET and Erk1/2 phosphorylation in the striatum. These increases were detected at 24 h and 48 h following LY379268 treatment. No changes were observed in the Akt and PLCg1 phosphorylation levels. Similar results for p-Erk1/2 were observed in the substantia nigra. A complete block of LY379268 effect on striatal RET and p-Erk1/2 phosphorylation was observed in mice intrastriatal injected with anti-GDNF antibodies, suggesting a correlation between GDNF upregulation and RET activation. Overall, with present data we have shown that activation of mGluR2/3 receptors by LY379268 may be particularly promising for nigrostriatal dopaminergic system protection by enhancing striatal levels of GDNF/RET trophic system activity.

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“…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: 73%

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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Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and -5 on astrocyte proliferation in culture

Cited by 92 publications

References 39 publications

Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Erk1/2 in mouse striatum

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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