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Cited by 105Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsPain Mechanisms and Treatments

Metabotropic Glutamate Receptors in Glial Cells: A New Potential Target for Neuroprotection?

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Spampinato, Simona Federica, Copani, Agata, Nicoletti, Ferdinando, Sortino, Maria Angela, Caraci, Filippo·2018·Frontiers in Molecular Neuroscience
DOI 10.3389/fnmol.2018.00414PMC PMC6243036
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Abstract

Neurodegenerative disorders are characterized by excitotoxicity and neuroinflammation that finally lead to slow neuronal degeneration and death. Although neurons are the principal target, glial cells are important players as they contribute by either exacerbating or dampening the events that lead to neuroinflammation and neuronal damage. A dysfunction of the glutamatergic system is a common event in the pathophysiology of these diseases. Metabotropic glutamate (mGlu) receptors belong to a large family of G protein-coupled receptors largely expressed in neurons as well as in glial cells. They often appear overexpressed in areas involved in neurodegeneration, where they can modulate glutamatergic transmission. Of note, mGlu receptor upregulation may involve microglia or, even more frequently, astrocytes, where their activation causes release of factors potentially able to influence neuronal death. The expression of mGlu receptors has been also reported on oligodendrocytes, a glial cell type specifically involved in the development of multiple sclerosis. Here we will provide a general overview on the possible involvement of mGlu receptors expressed on glial cells in the pathogenesis of different neurodegenerative disorders and the potential use of subtype-selective mGlu receptor ligands as candidate drugs for the treatment of neurodegenerative disorders. Negative allosteric modulators (NAM) of mGlu5 receptors might represent a relevant pharmacological tool to develop new neuroprotective strategies in these diseases. Recent evidence suggests that targeting astrocytes and microglia with positive allosteric modulators (PAM) of mGlu3 receptor or oligodendrocytes with mGlu4 PAMS might represent novel pharmacological approaches for the treatment of neurodegenerative disorders.

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  • miR-335, miR-1202, miR-29b-3p, and miR-134-5p may regulate depression through inhibiting GRM4 expression, affecting Ca2+ influx into prefrontal cortex neurons and extracellular glutamate concentration.

    “MiR-335, miR-1202, miR-29b-3p, and miR-134-5p may regulate depression through inhibiting the expression of GRM4 gene (Fig. 5), that in turn affect the influx of Ca2+ into the prefrontal cortex neurons and the extracellular concentration of glutamate.277–283”

    From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [278]

    The Group III mGlu Receptors section says mGlu4 receptor stimulation can alter astrocytic glutamate transport, supporting a limited link between this receptor and extracellular glutamate regulation. It does not link the four named miRNAs to GRM4 inhibition or depression, or describe the claimed Ca2+ influx in prefrontal cortex neurons (searched for the miRNAs, GRM4, depression, and prefrontal calcium influx). (LLM, conf=0.78)

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  1. Abdul-Ghani M. A. Valiante T. A. Carlen P. L. Pennefather P. S. (1996). Metabotropic glutamate receptors coupled to IP3 production mediate inhibition of IAHP in rat dentate granule neurons. J. Neurophysiol. 76 2691– 2700. 10.1152/jn.1996.76.4.2691 8899638 · DOI
  2. Agrawal S. K. Theriault E. Fehlings M. G. (1998). Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury. J. Neurotrauma 15 929– 941. 10.1089/neu.1998.15.929 9840766 · DOI
  3. Agulhon C. Petravicz J. McMullen A. B. Sweger E. J. Minton S. K. Taves S. R. (2008). What is the role of astrocyte calcium in neurophysiology? Neuron 59 932– 946. 10.1016/j.neuron.2008.09.004 18817732 PMC3623689 · DOI
  4. Anneser J. M. Chahli C. Ince P. G. Borasio G. D. Shaw P. J. (2004). Glial proliferation and metabotropic glutamate receptor expression in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 63 831– 840. 10.1093/jnen/63.8.831 15330338 · DOI
  5. Aronica E. Catania M. V. Geurts J. Yankaya B. Troost D. (2001). Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes. Neuroscience 105 509– 520. 10.1016/S0306-4522(01)00181-6 11672616 · DOI
  6. Aronica E. Gorter J. A. Ijlst-Keizers H. Rozemuller A. J. Yankaya B. Leenstra S. (2003a). Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur. J. Neurosci. 17 2106– 2118. 10.1046/j.1460-9568.2003.02657.x 12786977 · DOI
  7. Aronica E. Gorter J. A. Jansen G. H. van Veelen C. W. van Rijen P. C. Ramkema M. (2003b). Expression and cell distribution of group I and group II metabotropic glutamate receptor subtypes in taylor-type focal cortical dysplasia. Epilepsia 44 785– 795. 10.1046/j.1528-1157.2003.54802.x 12790891 · DOI
  8. Aronica E. Gorter J. A. Redeker S. Ramkema M. Spliet W. G. van Rijen P. C. (2005a). Distribution, characterization and clinical significance of microglia in glioneuronal tumours from patients with chronic intractable epilepsy. Neuropathol. Appl. Neurobiol. 31 280– 291. 10.1111/j.1365-2990.2004.00636.x 15885065 · DOI
  9. Aronica E. Gorter J. A. Rozemuller A. J. Yankaya B. Troost D. (2005b). Activation of metabotropic glutamate receptor 3 enhances interleukin (IL)-1beta-stimulated release of IL-6 in cultured human astrocytes. Neuroscience 130 927– 933. 10.1016/j.neuroscience.2004.10.024 15652990 · DOI
  10. Aronica E. Gorter J. A. Rozemuller A. J. Yankaya B. Troost D. (2005c). Interleukin-1 beta down-regulates the expression of metabotropic glutamate receptor 5 in cultured human astrocytes. J. Neuroimmunol. 160 188– 194. 10.1016/j.jneuroim.2004.11.015 15710472 · DOI
  11. Bakiri Y. Karadottir R. Cossell L. Attwell D. (2011). Morphological and electrical properties of oligodendrocytes in the white matter of the corpus callosum and cerebellum. J. Physiol. 589(Pt 3), 559– 573. 10.1113/jphysiol.2010.201376 21098009 PMC3055543 · DOI
  12. Balazs R. Miller S. Romano C. de Vries A. Chun Y. Cotman C. W. (1997). Metabotropic glutamate receptor mGluR5 in astrocytes: pharmacological properties and agonist regulation. J. Neurochem. 69 151– 163. 10.1046/j.1471-4159.1997.69010151.x 9202306 · DOI
  13. Barger S. W. Basile A. S. (2001). Activation of microglia by secreted amyloid precursor protein evokes release of glutamate by cystine exchange and attenuates synaptic function. J. Neurochem. 76 846– 854. 10.1046/j.1471-4159.2001.00075.x 11158256 · DOI
  14. Battaglia G. Busceti C. L. Molinaro G. Biagioni F. Traficante A. Nicoletti F. (2006). Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Neurosci. 26 7222– 7229. 10.1523/JNEUROSCI.1595-06.2006 16822979 PMC6673941 · DOI
  15. Battaglia G. Molinaro G. Riozzi B. Storto M. Busceti C. L. Spinsanti P. (2009). Activation of mGlu3 receptors stimulates the production of GDNF in striatal neurons. PLoS One 4: e6591. 10.1371/journal.pone.0006591 19672295 PMC2719807 · DOI
  16. Battaglia G. Riozzi B. Bucci D. Di Menna L. Molinaro G. Pallottino S. (2015). Activation of mGlu3 metabotropic glutamate receptors enhances GDNF and GLT-1 formation in the spinal cord and rescues motor neurons in the SOD-1 mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis. 74 126– 136. 10.1016/j.nbd.2014.11.012 25434487 · DOI
  17. Benatti C. Blom J. M. Rigillo G. Alboni S. Zizzi F. Torta R. (2016). Disease-induced neuroinflammation and depression. CNS Neurol. Disord. Drug Targets 15 414– 433. 10.2174/1871527315666160321104749 26996176 · DOI
  18. Beneventano M. Spampinato S. F. Merlo S. Chisari M. Platania P. Ragusa M. (2017). Shedding of microvesicles from microglia contributes to the effects induced by metabotropic glutamate receptor 5 activation on neuronal death. Front. Pharmacol. 8: 812. 10.3389/fphar.2017.00812 29170640 PMC5684115 · DOI
  19. Berger J. V. Dumont A. O. Focant M. C. Vergouts M. Sternotte A. Calas A. G. (2012). Opposite regulation of metabotropic glutamate receptor 3 and metabotropic glutamate receptor 5 by inflammatory stimuli in cultured microglia and astrocytes. Neuroscience 205 29– 38. 10.1016/j.neuroscience.2011.12.044 22245498 · DOI
  20. Besong G. Battaglia G. D’Onofrio M. Di Marco R. Ngomba R. T. Storto M. (2002). Activation of group III metabotropic glutamate receptors inhibits the production of RANTES in glial cell cultures. J. Neurosci. 22 5403– 5411. 10.1523/JNEUROSCI.22-13-05403.2002 12097492 PMC6758236 · DOI
  21. Betts M. J. O’Neill M. J. Duty S. (2012). Allosteric modulation of the group III mGlu4 receptor provides functional neuroprotection in the 6-hydroxydopamine rat model of Parkinson’s disease. Br. J. Pharmacol. 166 2317– 2330. 10.1111/j.1476-5381.2012.01943.x 22404342 PMC3448896 · DOI
  22. Block M. L. Hong J. S. (2007). Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem. Soc. Trans. 35(Pt 5), 1127– 1132. 10.1042/BST0351127 17956294 · DOI
  23. Blumcke I. Behle K. Malitschek B. Kuhn R. Knopfel T. Wolf H. K. (1996). Immunohistochemical distribution of metabotropic glutamate receptor subtypes mGluR1b, mGluR2/3, mGluR4a and mGluR5 in human hippocampus. Brain Res. 736 217– 226. 10.1016/0006-8993(96)00697-X 8930327 · DOI
  24. Boer K. Encha-Razavi F. Sinico M. Aronica E. (2010). Differential distribution of group I metabotropic glutamate receptors in developing human cortex. Brain Res. 1324 24– 33. 10.1016/j.brainres.2010.02.005 20149785 · DOI
  25. Bond A. Jones N. M. Hicks C. A. Whiffin G. M. Ward M. A. O’Neill M. F. (2000). Neuroprotective effects of LY379268, a selective mGlu2/3 receptor agonist: investigations into possible mechanism of action in vivo. J. Pharmacol. Exp. Ther. 294 800– 809. 10945827
  26. Bond A. O’Neill M. J. Hicks C. A. Monn J. A. Lodge D. (1998). Neuroprotective effects of a systemically active group II metabotropic glutamate receptor agonist LY354740 in a gerbil model of global ischaemia. Neuroreport 9 1191– 1193. 10.1097/00001756-199804200-00042 9601692 · DOI
  27. Bonde C. Sarup A. Schousboe A. Gegelashvili G. Zimmer J. Noraberg J. (2003). Neurotoxic and neuroprotective effects of the glutamate transporter inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) during physiological and ischemia-like conditions. Neurochem. Int. 43 371– 380. 10.1016/S0197-0186(03)00024-X 12742081 · DOI
  28. Bradley S. J. Challiss R. A. (2011). Defining protein kinase/phosphatase isoenzymic regulation of mGlu(5) receptor-stimulated phospholipase C and Ca2+ responses in astrocytes. Br. J. Pharmacol. 164 755– 771. 10.1111/j.1476-5381.2011.01421.x 21486279 PMC3188889 · DOI
  29. Bruno V. Battaglia G. Casabona G. Copani A. Caciagli F. Nicoletti F. (1998). Neuroprotection by glial metabotropic glutamate receptors is mediated by transforming growth factor-beta. J. Neurosci. 18 9594– 9600. 10.1523/JNEUROSCI.18-23-09594.1998 9822720 PMC6793276 · DOI
  30. Bruno V. Caraci F. Copani A. Matrisciano F. Nicoletti F. Battaglia G. (2017). The impact of metabotropic glutamate receptors into active neurodegenerative processes: a “dark side” in the development of new symptomatic treatments for neurologic and psychiatric disorders. Neuropharmacology 115 180– 192. 10.1016/j.neuropharm.2016.04.044 27140693 · DOI
  31. Butt A. M. Vanzulli I. Papanikolaou M. De La Rocha I. C. Hawkins V. E. (2017). Metabotropic glutamate receptors protect oligodendrocytes from acute ischemia in the mouse optic nerve. Neurochem. Res. 42 2468– 2478. 10.1007/s11064-017-2220-1 28365868 PMC5603641 · DOI
  32. Byrnes K. R. Loane D. J. Stoica B. A. Zhang J. Faden A. I. (2012). Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury. J. Neuroinflammation 9: 43. 10.1186/1742-2094-9-43 22373400 PMC3308916 · DOI
  33. Byrnes K. R. Stoica B. Loane D. J. Riccio A. Davis M. I. Faden A. I. (2009). Metabotropic glutamate receptor 5 activation inhibits microglial associated inflammation and neurotoxicity. Glia 57 550– 560. 10.1002/glia.20783 18816644 PMC2644739 · DOI
  34. Cai Z. Schools G. P. Kimelberg H. K. (2000). Metabotropic glutamate receptors in acutely isolated hippocampal astrocytes: developmental changes of mGluR5 mRNA and functional expression. Glia 29 70– 80. 10.1002/(SICI)1098-1136(20000101)29:1<70::AID-GLIA7>3.0.CO;2-V 10594924 · DOI
  35. Caraci F. Gulisano W. Guida C. A. Impellizzeri A. A. Drago F. Puzzo D. (2015). A key role for TGF-beta1 in hippocampal synaptic plasticity and memory. Sci. Rep. 5: 11252. 10.1038/srep11252 26059637 PMC4462026 · DOI
  36. Caraci F. Molinaro G. Battaglia G. Giuffrida M. L. Riozzi B. Traficante A. (2011). Targeting group II metabotropic glutamate (mGlu) receptors for the treatment of psychosis associated with Alzheimer’s disease: selective activation of mGlu2 receptors amplifies beta-amyloid toxicity in cultured neurons, whereas dual activation of mGlu2 and mGlu3 receptors is neuroprotective. Mol. Pharmacol. 79 618– 626. 10.1124/mol.110.067488 21159998 · DOI
  37. Caraci F. Nicoletti F. Copani A. (2018a). Metabotropic glutamate receptors: the potential for therapeutic applications in Alzheimer’s disease. Curr. Opin. Pharmacol. 38 1– 7. 10.1016/j.coph.2017.12.001 29278824 · DOI · Paper page
  38. Caraci F. Spampinato S. Sortino M. A. Bosco P. Battaglia G. Bruno V. (2012). Dysfunction of TGF-beta1 signaling in Alzheimer’s disease: perspectives for neuroprotection. Cell Tissue Res. 347 291– 301. 10.1007/s00441-011-1230-6 21879289 · DOI
  39. Casley C. S. Lakics V. Lee H. G. Broad L. M. Day T. A. Cluett T. (2009). Up-regulation of astrocyte metabotropic glutamate receptor 5 by amyloid-beta peptide. Brain Res. 1260 65– 75. 10.1016/j.brainres.2008.12.082 19401173 · DOI
  40. Cha J. H. Farrell L. A. Ahmed S. F. Frey A. Hsiao-Ashe K. K. Young A. B. (2001). Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor protein. Neurobiol. Dis. 8 90– 102. 10.1006/nbdi.2000.0330 11162243 · DOI
  41. Chiechio S. (2016). Modulation of chronic pain by metabotropic glutamate receptors. Adv. Pharmacol. 75 63– 89. 10.1016/bs.apha.2015.11.001 26920009 · DOI
  42. Ciccarelli R. D’Alimonte I. Ballerini P. D’Auro M. Nargi E. Buccella S. (2007). Molecular signalling mediating the protective effect of A1 adenosine and mGlu3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. Mol. Pharmacol. 71 1369– 1380. 10.1124/mol.106.031617 17293559 · DOI
  43. Ciccarelli R. Di Iorio P. Bruno V. Battaglia G. D’Alimonte I. D’Onofrio M. (1999). Activation of A(1) adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100beta protein from cultured astrocytes. Glia 27 275– 281. 10.1002/(SICI)1098-1136(199909)27:3<275::AID-GLIA9>3.0.CO;2-0 10457374 · DOI
  44. Ciccarelli R. Sureda F. X. Casabona G. Di Iorio P. Caruso A. Spinella F. (1997). Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and -5 on astrocyte proliferation in culture. Glia 21 390– 398. 10.1002/(SICI)1098-1136(199712)21:4<390::AID-GLIA6>3.0.CO;2-7 9419014 · DOI
  45. Conn P. J. Pin J. P. (1997). Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol. 37 205– 237. 10.1146/annurev.pharmtox.37.1.205 9131252 · DOI
  46. Corti C. Battaglia G. Molinaro G. Riozzi B. Pittaluga A. Corsi M. (2007). The use of knock-out mice unravels distinct roles for mGlu2 and mGlu3 metabotropic glutamate receptors in mechanisms of neurodegeneration/neuroprotection. J. Neurosci. 27 8297– 8308. 10.1523/JNEUROSCI.1889-07.2007 17670976 PMC6673047 · DOI
  47. D’Antoni S. Berretta A. Seminara G. Longone P. Giuffrida-Stella A. M. Battaglia G. (2011). A prolonged pharmacological blockade of type-5 metabotropic glutamate receptors protects cultured spinal cord motor neurons against excitotoxic death. Neurobiol. Dis. 42 252– 264. 10.1016/j.nbd.2011.01.013 21232601 · DOI
  48. Deng W. Rosenberg P. A. Volpe J. J. Jensen F. E. (2003). Calcium-permeable AMPA/kainate receptors mediate toxicity and preconditioning by oxygen-glucose deprivation in oligodendrocyte precursors. Proc. Natl. Acad. Sci. U.S.A. 100 6801– 6806. 10.1073/pnas.1136624100 12743362 PMC164527 · DOI
  49. Deng W. Wang H. Rosenberg P. A. Volpe J. J. Jensen F. E. (2004). Role of metabotropic glutamate receptors in oligodendrocyte excitotoxicity and oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 101 7751– 7756. 10.1073/pnas.0307850101 15136737 PMC419678 · DOI
  50. Dewapriya P. Li Y. X. Himaya S. W. Pangestuti R. Kim S. K. (2013). Neoechinulin A suppresses amyloid-beta oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity. Neurotoxicology 35 30– 40. 10.1016/j.neuro.2012.12.004 23261590 · DOI
  51. Dewar D. Chalmers D. T. Graham D. I. McCulloch J. (1991). Glutamate metabotropic and AMPA binding sites are reduced in Alzheimer’s disease: an autoradiographic study of the hippocampus. Brain Res. 553 58– 64. 10.1016/0006-8993(91)90230-S 1933277 · DOI
  52. Ding S. Fellin T. Zhu Y. Lee S. Y. Auberson Y. P. Meaney D. F. (2007). Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus. J. Neurosci. 27 10674– 10684. 10.1523/JNEUROSCI.2001-07.2007 17913901 PMC2917229 · DOI
  53. Doble A. (1999). The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol. Ther. 81 163– 221. 10.1016/S0163-7258(98)00042-4 10334661 · DOI · Paper page
  54. Drouin-Ouellet J. Brownell A. L. Saint-Pierre M. Fasano C. Emond V. Trudeau L. E. (2011). Neuroinflammation is associated with changes in glial mGluR5 expression and the development of neonatal excitotoxic lesions. Glia 59 188– 199. 10.1002/glia.21086 21125661 PMC3983848 · DOI
  55. Dugan L. L. Choi D. W. (1994). Excitotoxicity, free radicals, and cell membrane changes. Ann. Neurol. 35(Suppl.), S17– S21. 10.1002/ana.410350707 8185290 · DOI
  56. Durand D. Carniglia L. Beauquis J. Caruso C. Saravia F. Lasaga M. (2014). Astroglial mGlu3 receptors promote alpha-secretase-mediated amyloid precursor protein cleavage. Neuropharmacology 79 180– 189. 10.1016/j.neuropharm.2013.11.015 24291464 · DOI
  57. Durand D. Carniglia L. Caruso C. Lasaga M. (2013). mGlu3 receptor and astrocytes: partners in neuroprotection. Neuropharmacology 66 1– 11. 10.1016/j.neuropharm.2012.04.009 22564439 · DOI
  58. Durand D. Carniglia L. Turati J. Ramirez D. Saba J. Caruso C. (2017). Amyloid-beta neurotoxicity and clearance are both regulated by glial group II metabotropic glutamate receptors. Neuropharmacology 123 274– 286. 10.1016/j.neuropharm.2017.05.008 28495373 · DOI
  59. Durand D. Caruso C. Carniglia L. Lasaga M. (2010). Metabotropic glutamate receptor 3 activation prevents nitric oxide-induced death in cultured rat astrocytes. J. Neurochem. 112 420– 433. 10.1111/j.1471-4159.2009.06469.x 20085613 · DOI
  60. Ettle B. Schlachetzki J. C. M. Winkler J. (2016). Oligodendroglia and myelin in neurodegenerative diseases: more than just bystanders? Mol. Neurobiol. 53 3046– 3062. 10.1007/s12035-015-9205-3 25966971 PMC4902834 · DOI · Paper page
  61. Fallarino F. Volpi C. Fazio F. Notartomaso S. Vacca C. Busceti C. (2010). Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation. Nat. Med. 16 897– 902. 10.1038/nm.2183 20657581 · DOI
  62. Farso M. C. O’Shea R. D. Beart P. M. (2009). Evidence group I mGluR drugs modulate the activation profile of lipopolysaccharide-exposed microglia in culture. Neurochem. Res. 34 1721– 1728. 10.1007/s11064-009-9999-3 19479374 · DOI
  63. Fazio F. Ulivieri M. Volpi C. Gargaro M. Fallarino F. (2018). Targeting metabotropic glutamate receptors for the treatment of neuroinflammation. Curr. Opin. Pharmacol. 38 16– 23. 10.1016/j.coph.2018.01.010 29471184 · DOI
  64. Fazio F. Zappulla C. Notartomaso S. Busceti C. Bessede A. Scarselli P. (2014). Cinnabarinic acid, an endogenous agonist of type-4 metabotropic glutamate receptor, suppresses experimental autoimmune encephalomyelitis in mice. Neuropharmacology 81 237– 243. 10.1016/j.neuropharm.2014.02.011 24565643 · DOI
  65. Fellner L. Stefanova N. (2013). The role of glia in alpha-synucleinopathies. Mol. Neurobiol. 47 575– 586. 10.1007/s12035-012-8340-3 22941028 PMC3589649 · DOI
  66. Fern R. F. Matute C. Stys P. K. (2014). White matter injury: ischemic and nonischemic. Glia 62 1780– 1789. 10.1002/glia.22722 25043122 · DOI
  67. Ferrer I. (2018). Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: the forgotten partner. Prog. Neurobiol. 169 24– 54. 10.1016/j.pneurobio.2018.07.004 30077775 · DOI
  68. Fiacco T. A. Agulhon C. McCarthy K. D. (2009). Sorting out astrocyte physiology from pharmacology. Annu. Rev. Pharmacol. Toxicol. 49 151– 174. 10.1146/annurev.pharmtox.011008.145602 18834310 · DOI
  69. Gegelashvili G. Dehnes Y. Danbolt N. C. Schousboe A. (2000). The high-affinity glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Neurochem. Int. 37 163– 170. 10.1016/S0197-0186(00)00019-X 10812201 · DOI
  70. Gerber U. Gee C. E. Benquet P. (2007). Metabotropic glutamate receptors: intracellular signaling pathways. Curr. Opin. Pharmacol. 7 56– 61. 10.1016/j.coph.2006.08.008 17055336 · DOI
  71. Geurts J. J. Wolswijk G. Bo L. Redeker S. Ramkema M. Troost D. (2005). Expression patterns of Group III metabotropic glutamate receptors mGluR4 and mGluR8 in multiple sclerosis lesions. J. Neuroimmunol. 158 182– 190. 10.1016/j.jneuroim.2004.08.012 15589052 · DOI
  72. Geurts J. J. Wolswijk G. Bo L. van der Valk P. Polman C. H. Troost D. (2003). Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis. Brain 126(Pt 8), 1755– 1766. 10.1093/brain/awg179 12805104 · DOI
  73. Giordano C. Cristino L. Luongo L. Siniscalco D. Petrosino S. Piscitelli F. (2012). TRPV1-dependent and -independent alterations in the limbic cortex of neuropathic mice: impact on glial caspases and pain perception. Cereb. Cortex 22 2495– 2518. 10.1093/cercor/bhr328 22139792 PMC3464411 · DOI
  74. Guida F. Luongo L. Marmo F. Romano R. Iannotta M. Napolitano F. (2015). Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice. Mol. Brain 8: 47. 10.1186/s13041-015-0139-5 26260027 PMC4532244 · DOI
  75. Gwak Y. S. Hulsebosch C. E. (2005). Upregulation of Group I metabotropic glutamate receptors in neurons and astrocytes in the dorsal horn following spinal cord injury. Exp. Neurol. 195 236– 243. 10.1016/j.expneurol.2005.05.012 16004983 · DOI
  76. Hamilton N. Vayro S. Wigley R. Butt A. M. (2010). Axons and astrocytes release ATP and glutamate to evoke calcium signals in NG2-glia. Glia 58 66– 79. 10.1002/glia.20902 19533604 · DOI
  77. Hardingham G. E. Bading H. (2003). The Yin and Yang of NMDA receptor signalling. Trends Neurosci. 26 81– 89. 10.1016/S0166-2236(02)00040-1 12536131 · DOI
  78. Hathaway H. A. Pshenichkin S. Grajkowska E. Gelb T. Emery A. C. Wolfe B. B. (2015). Pharmacological characterization of mGlu1 receptors in cerebellar granule cells reveals biased agonism. Neuropharmacology 93 199– 208. 10.1016/j.neuropharm.2015.02.007 25700650 PMC4387075 · DOI
  79. Hellyer S. Leach K. Gregory K. J. (2017). Neurobiological insights and novel therapeutic opportunities for CNS disorders from mGlu receptor allosteric and biased modulation. Curr. Opin. Pharmacol. 32 49– 55. 10.1016/j.coph.2016.10.007 27842256 · DOI
  80. Heneka M. T. Rodriguez J. J. Verkhratsky A. (2010). Neuroglia in neurodegeneration. Brain Res. Rev. 63 189– 211. 10.1016/j.brainresrev.2009.11.004 19944719 · DOI
  81. Homayoun H. Moghaddam B. (2010). Group 5 metabotropic glutamate receptors: role in modulating cortical activity and relevance to cognition. Eur. J. Pharmacol. 639 33– 39. 10.1016/j.ejphar.2009.12.042 20371231 · DOI
  82. Hossain M. Z. Unno S. Ando H. Masuda Y. Kitagawa J. (2017). Neuron-glia crosstalk and neuropathic pain: involvement in the modulation of motor activity in the orofacial region. Int. J. Mol. Sci. 18: E2051. 10.3390/ijms18102051 28954391 PMC5666733 · DOI
  83. Huang Y. Y. Zhang Q. Zhang J. N. Zhang Y. N. Gu L. Yang H. M. (2018). Triptolide up-regulates metabotropic glutamate receptor 5 to inhibit microglia activation in the lipopolysaccharide-induced model of Parkinson’s disease. Brain Behav. Immun. 71 93– 107. 10.1016/j.bbi.2018.04.006 29649522 · DOI
  84. Iacovelli L. Bruno V. Salvatore L. Melchiorri D. Gradini R. Caricasole A. (2002). Native group-III metabotropic glutamate receptors are coupled to the mitogen-activated protein kinase/phosphatidylinositol-3-kinase pathways. J. Neurochem. 82 216– 223. 10.1046/j.1471-4159.2002.00929.x 12124422 · DOI
  85. Iacovelli L. Felicioni M. Nistico R. Nicoletti F. De Blasi A. (2014). Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins. Neuropharmacology 77 303– 312. 10.1016/j.neuropharm.2013.10.013 24148810 · DOI
  86. Ibanez C. F. Andressoo J. O. (2017). Biology of GDNF and its receptors - Relevance for disorders of the central nervous system. Neurobiol. Dis. 97(Pt B), 80– 89. 10.1016/j.nbd.2016.01.021 26829643 · DOI
  87. Iyer A. M. van Scheppingen J. Milenkovic I. Anink J. J. Lim D. Genazzani A. A. (2014). Metabotropic glutamate receptor 5 in Down’s syndrome hippocampus during development: increased expression in astrocytes. Curr. Alzheimer Res. 11 694– 705. 10.2174/1567205011666140812115423 25115540 · DOI
  88. Jantas D. Lech T. Golda S. Pilc A. Lason W. (2018). New evidences for a role of mGluR7 in astrocyte survival: possible implications for neuroprotection. Neuropharmacology 141 223– 237. 10.1016/j.neuropharm.2018.08.035 30170084 · DOI
  89. Jantzie L. L. Talos D. M. Selip D. B. An L. Jackson M. C. Folkerth R. D. (2010). Developmental regulation of group I metabotropic glutamate receptors in the premature brain and their protective role in a rodent model of periventricular leukomalacia. Neuron Glia Biol. 6 277– 288. 10.1017/S1740925X11000111 22169210 PMC6732218 · DOI
  90. Ji R. R. Xu Z. Z. Gao Y. J. (2014). Emerging targets in neuroinflammation-driven chronic pain. Nat. Rev. Drug Discov. 13 533– 548. 10.1038/nrd4334 24948120 PMC4228377 · DOI
  91. Kammermeier P. J. (2012). Functional and pharmacological characteristics of metabotropic glutamate receptors 2/4 heterodimers. Mol. Pharmacol. 82 438– 447. 10.1124/mol.112.078501 22653971 PMC3422699 · DOI
  92. Kaushal V. Schlichter L. C. (2008). Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke penumbra. J. Neurosci. 28 2221– 2230. 10.1523/JNEUROSCI.5643-07.2008 18305255 PMC6671848 · DOI
  93. Kelland E. E. Toms N. J. (2001). Group I metabotropic glutamate receptors limit AMPA receptor-mediated oligodendrocyte progenitor cell death. Eur. J. Pharmacol. 424 R3– R4. 10.1016/S0014-2999(01)01157-8 11672568 · DOI
  94. Kim S. U. de Vellis J. (2005). Microglia in health and disease. J. Neurosci. Res. 81 302– 313. 10.1002/jnr.20562 15954124 · DOI
  95. Klaver R. De Vries H. E. Schenk G. J. Geurts J. J. (2013). Grey matter damage in multiple sclerosis: a pathology perspective. Prion 7 66– 75. 10.4161/pri.23499 23324595 PMC3609053 · DOI
  96. Kobayashi K. Hayashi M. Nakano H. Fukutani Y. Sasaki K. Shimazaki M. (2002). Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in white matter lesions in Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 28 238– 251. 10.1046/j.1365-2990.2002.00390.x 12060348 · DOI
  97. Le Poul E. Bolea C. Girard F. Poli S. Charvin D. Campo B. (2012). A potent and selective metabotropic glutamate receptor 4 positive allosteric modulator improves movement in rodent models of Parkinson’s disease. J. Pharmacol. Exp. Ther. 343 167– 177. 10.1124/jpet.112.196063 22787118 · DOI
  98. Liu F. Zhou R. Yan H. Yin H. Wu X. Tan Y. (2014). Metabotropic glutamate receptor 5 modulates calcium oscillation and innate immune response induced by lipopolysaccharide in microglial cell. Neuroscience 281 24– 34. 10.1016/j.neuroscience.2014.09.034 25250840 · DOI
  99. Liu G. J. Nagarajah R. Banati R. B. Bennett M. R. (2009). Glutamate induces directed chemotaxis of microglia. Eur. J. Neurosci. 29 1108– 1118. 10.1111/j.1460-9568.2009.06659.x 19302147 · DOI
  100. Loane D. J. Stoica B. A. Pajoohesh-Ganji A. Byrnes K. R. Faden A. I. (2009). Activation of metabotropic glutamate receptor 5 modulates microglial reactivity and neurotoxicity by inhibiting NADPH oxidase. J. Biol. Chem. 284 15629– 15639. 10.1074/jbc.M806139200 19364772 PMC2708859 · DOI
  101. Loane D. J. Stoica B. A. Tchantchou F. Kumar A. Barrett J. P. Akintola T. (2014). Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental traumatic brain injury. Neurotherapeutics 11 857– 869. 10.1007/s13311-014-0298-6 25096154 PMC4391388 · DOI
  102. Lujan R. Shigemoto R. Lopez-Bendito G. (2005). Glutamate and GABA receptor signalling in the developing brain. Neuroscience 130 567– 580. 10.1016/j.neuroscience.2004.09.042 15590141 · DOI
  103. Luyt K. Varadi A. Durant C. F. Molnar E. (2006). Oligodendroglial metabotropic glutamate receptors are developmentally regulated and involved in the prevention of apoptosis. J. Neurochem. 99 641– 656. 10.1111/j.1471-4159.2006.04103.x 16836654 · DOI
  104. Luyt K. Varadi A. Molnar E. (2003). Functional metabotropic glutamate receptors are expressed in oligodendrocyte progenitor cells. J. Neurochem. 84 1452– 1464. 10.1046/j.1471-4159.2003.01661.x 12614345 · DOI
  105. Macrez R. Stys P. K. Vivien D. Lipton S. A. Docagne F. (2016). Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities. Lancet Neurol. 15 1089– 1102. 10.1016/S1474-4422(16)30165-X 27571160 · DOI
  106. Martin G. M. (2000). Molecular mechanisms of late life dementias. Exp. Gerontol. 35 439– 443. 10.1016/S0531-5565(99)00090-X 10959031 · DOI
  107. Mastroiacovo F. Moyanova S. Cannella M. Gaglione A. Verhaeghe R. Bozza G. (2017). Genetic deletion of mGlu2 metabotropic glutamate receptors improves the short-term outcome of cerebral transient focal ischemia. Mol. Brain 10: 39. 10.1186/s13041-017-0319-6 28821279 PMC5562974 · DOI
  108. McMullan S. M. Phanavanh B. Li G. G. Barger S. W. (2012). Metabotropic glutamate receptors inhibit microglial glutamate release. ASN Neuro 4: e00094. 10.1042/AN20120044 22770428 PMC3413012 · DOI
  109. Miller S. Romano C. Cotman C. W. (1995). Growth factor upregulation of a phosphoinositide-coupled metabotropic glutamate receptor in cortical astrocytes. J. Neurosci. 15 6103– 6109. 10.1523/JNEUROSCI.15-09-06103.1995 7666194 PMC6577656 · DOI
  110. Mosher K. I. Wyss-Coray T. (2014). Microglial dysfunction in brain aging and Alzheimer’s disease. Biochem. Pharmacol. 88 594– 604. 10.1016/j.bcp.2014.01.008 24445162 PMC3972294 · DOI · Paper page
  111. Motolese M. Mastroiacovo F. Cannella M. Bucci D. Gaglione A. Riozzi B. (2015). Targeting type-2 metabotropic glutamate receptors to protect vulnerable hippocampal neurons against ischemic damage. Mol. Brain 8: 66. 10.1186/s13041-015-0158-2 26496940 PMC4619332 · DOI
  112. Nakamichi N. Yoshida K. Ishioka Y. Makanga J. O. Fukui M. Yoneyama M. (2008). Group III metabotropic glutamate receptor activation suppresses self-replication of undifferentiated neocortical progenitor cells. J. Neurochem. 105 1996– 2012. 10.1111/j.1471-4159.2008.05289.x 18266930 · DOI
  113. Newcombe J. Uddin A. Dove R. Patel B. Turski L. Nishizawa Y. (2008). Glutamate receptor expression in multiple sclerosis lesions. Brain Pathol. 18 52– 61. 10.1111/j.1750-3639.2007.00101.x 17924980 PMC8095601 · DOI
  114. Nguyen D. Alavi M. V. Kim K. Y. Kang T. Scott R. T. Noh Y. H. (2011). A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics. Cell Death Dis. 2: e240. 10.1038/cddis.2011.117 22158479 PMC3252734 · DOI
  115. Nicoletti F. Bockaert J. Collingridge G. L. Conn P. J. Ferraguti F. Schoepp D. D. (2011). Metabotropic glutamate receptors: from the workbench to the bedside. Neuropharmacology 60 1017– 1041. 10.1016/j.neuropharm.2010.10.022 21036182 PMC3787883 · DOI
  116. Niswender C. M. Conn P. J. (2010). Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol. 50 295– 322. 10.1146/annurev.pharmtox.011008.145533 20055706 PMC2904507 · DOI
  117. Oliet S. H. Piet R. Poulain D. A. (2001). Control of glutamate clearance and synaptic efficacy by glial coverage of neurons. Science 292 923– 926. 10.1126/science.1059162 11340204 · DOI
  118. Olmos G. Llado J. (2014). Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators Inflamm. 2014: 861231. 10.1155/2014/861231 24966471 PMC4055424 · DOI · Paper page
  119. O’Riordan K. J. Huang I. C. Pizzi M. Spano P. Boroni F. Egli R. (2006). Regulation of nuclear factor kappaB in the hippocampus by group I metabotropic glutamate receptors. J. Neurosci. 26 4870– 4879. 10.1523/JNEUROSCI.4527-05.2006 16672661 PMC6674168 · DOI
  120. Palazzo E. Marabese I. Luongo L. Guida F. de Novellis V. Maione S. (2017). Nociception modulation by supraspinal group III metabotropic glutamate receptors. J. Neurochem. 141 507– 519. 10.1111/jnc.13725 27363363 · DOI
  121. Paquet M. Ribeiro F. M. Guadagno J. Esseltine J. L. Ferguson S. S. Cregan S. P. (2013). Role of metabotropic glutamate receptor 5 signaling and homer in oxygen glucose deprivation-mediated astrocyte apoptosis. Mol. Brain 6: 9. 10.1186/1756-6606-6-9 23406666 PMC3598502 · DOI
  122. Pickering M. Cumiskey D. O’Connor J. J. (2005). Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp. Physiol. 90 663– 670. 10.1113/expphysiol.2005.030734 15944202 · DOI
  123. Piers T. M. Heales S. J. Pocock J. M. (2011). Positive allosteric modulation of metabotropic glutamate receptor 5 down-regulates fibrinogen-activated microglia providing neuronal protection. Neurosci. Lett. 505 140– 145. 10.1016/j.neulet.2011.10.007 22015768 · DOI
  124. Pin J. P. Bettler B. (2016). Organization and functions of mGlu and GABAB receptor complexes. Nature 540 60– 68. 10.1038/nature20566 27905440 · DOI
  125. Pinteaux-Jones F. Sevastou I. G. Fry V. A. Heales S. Baker D. Pocock J. M. (2008). Myelin-induced microglial neurotoxicity can be controlled by microglial metabotropic glutamate receptors. J. Neurochem. 106 442– 454. 10.1111/j.1471-4159.2008.05426.x 18419765 · DOI
  126. Ponnazhagan R. Harms A. S. Thome A. D. Jurkuvenaite A. Gogliotti R. Niswender C. M. (2016). The metabotropic glutamate receptor 4 positive allosteric modulator ADX88178 inhibits inflammatory responses in primary microglia. J. Neuroimmune Pharmacol. 11 231– 237. 10.1007/s11481-016-9655-z 26872456 PMC4848139 · DOI
  127. Ribeiro F. M. Vieira L. B. Pires R. G. Olmo R. P. Ferguson S. S. (2017). Metabotropic glutamate receptors and neurodegenerative diseases. Pharmacol. Res. 115 179– 191. 10.1016/j.phrs.2016.11.013 27872019 · DOI
  128. Rodriguez-Kern A. Gegelashvili M. Schousboe A. Zhang J. Sung L. Gegelashvili G. (2003). Beta-amyloid and brain-derived neurotrophic factor, BDNF, up-regulate the expression of glutamate transporter GLT-1/EAAT2 via different signaling pathways utilizing transcription factor NF-κB. Neurochem. Int. 43 363– 370. 10.1016/s0197-0186(03)00023-8 12742080 · DOI
  129. Romano C. Smout S. Miller J. K. O’Malley K. L. (2002). Developmental regulation of metabotropic glutamate receptor 5b protein in rodent brain. Neuroscience 111 693– 698. 10.1016/S0306-4522(02)00042-8 12031354 · DOI
  130. Rosenbluth J. (2009). Multiple functions of the paranodal junction of myelinated nerve fibers. J. Neurosci. Res. 87 3250– 3258. 10.1002/jnr.22013 19224642 · DOI
  131. Rossi D. J. Oshima T. Attwell D. (2000). Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403 316– 321. 10.1038/35002090 10659851 · DOI
  132. Rothstein J. D. Van Kammen M. Levey A. I. Martin L. J. Kuncl R. W. (1995). Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol. 38 73– 84. 10.1002/ana.410380114 7611729 · DOI · Paper page
  133. Shah A. Silverstein P. S. Singh D. P. Kumar A. (2012). Involvement of metabotropic glutamate receptor 5, AKT/PI3K signaling and NF-kappaB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes. J. Neuroinflammation 9: 52. 10.1186/1742-2094-9-52 22420994 PMC3338363 · DOI
  134. Shrivastava A. N. Kowalewski J. M. Renner M. Bousset L. Koulakoff A. Melki R. (2013). beta-amyloid and ATP-induced diffusional trapping of astrocyte and neuronal metabotropic glutamate type-5 receptors. Glia 61 1673– 1686. 10.1002/glia.22548 23922225 · DOI
  135. Sorensen T. L. Tani M. Jensen J. Pierce V. Lucchinetti C. Folcik V. A. (1999). Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J. Clin. Invest. 103 807– 815. 10.1172/JCI5150 10079101 PMC408141 · DOI
  136. Spampinato S. F. Merlo S. Chisari M. Nicoletti F. Sortino M. A. (2014). Glial metabotropic glutamate receptor-4 increases maturation and survival of oligodendrocytes. Front. Cell. Neurosci. 8: 462. 10.3389/fncel.2014.00462 25642169 PMC4294134 · DOI
  137. Spampinato S. F. Merlo S. Molinaro G. Battaglia G. Bruno V. Nicoletti F. (2012a). Dual effect of 17beta-estradiol on NMDA-induced neuronal death: involvement of metabotropic glutamate receptor 1. Endocrinology 153 5940– 5948. 10.1210/en.2012-1799 23077075 · DOI
  138. Spampinato S. F. Molinaro G. Merlo S. Iacovelli L. Caraci F. Battaglia G. (2012b). Estrogen receptors and type 1 metabotropic glutamate receptors are interdependent in protecting cortical neurons against beta-amyloid toxicity. Mol. Pharmacol. 81 12– 20. 10.1124/mol.111.074021 21984253 · DOI
  139. Stevens B. Allen N. J. Vazquez L. E. Howell G. R. Christopherson K. S. Nouri N. (2007). The classical complement cascade mediates CNS synapse elimination. Cell 131 1164– 1178. 10.1016/j.cell.2007.10.036 18083105 · DOI · Paper page
  140. Strachan-Whaley M. Rivest S. Yong V. W. (2014). Interactions between microglia and T cells in multiple sclerosis pathobiology. J. Interferon Cytokine Res. 34 615– 622. 10.1089/jir.2014.0019 25084178 · DOI
  141. Streit W. J. Xue Q. S. (2014). Human CNS immune senescence and neurodegeneration. Curr. Opin. Immunol. 29 93– 96. 10.1016/j.coi.2014.05.005 24908174 · DOI · Paper page
  142. Sun W. McConnell E. Pare J. F. Xu Q. Chen M. Peng W. (2013). Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science 339 197– 200. 10.1126/science.1226740 23307741 PMC3569008 · DOI
  143. Tang F. R. Lee W. L. (2001). Expression of the group II and III metabotropic glutamate receptors in the hippocampus of patients with mesial temporal lobe epilepsy. J. Neurocytol. 30 137– 143. 10.1023/A:1011939223872 11577252 · DOI
  144. Taylor D. L. Diemel L. T. Cuzner M. L. Pocock J. M. (2002). Activation of group II metabotropic glutamate receptors underlies microglial reactivity and neurotoxicity following stimulation with chromogranin A, a peptide up-regulated in Alzheimer’s disease. J. Neurochem. 82 1179– 1191. 10.1046/j.1471-4159.2002.01062.x 12358765 · DOI
  145. Taylor D. L. Diemel L. T. Pocock J. M. (2003). Activation of microglial group III metabotropic glutamate receptors protects neurons against microglial neurotoxicity. J. Neurosci. 23 2150– 2160. 10.1523/JNEUROSCI.23-06-02150.2003 12657674 PMC6742009 · DOI
  146. Taylor D. L. Jones F. Kubota E. S. Pocock J. M. (2005). Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. J. Neurosci. 25 2952– 2964. 10.1523/JNEUROSCI.4456-04.2005 15772355 PMC6725132 · DOI · Paper page
  147. Tichauer J. E. von Bernhardi R. (2012). Transforming growth factor-beta stimulates beta amyloid uptake by microglia through Smad3-dependent mechanisms. J. Neurosci. Res. 90 1970– 1980. 10.1002/jnr.23082 22715062 · DOI
  148. Tilleux S. Berger J. Hermans E. (2007). Induction of astrogliosis by activated microglia is associated with a down-regulation of metabotropic glutamate receptor 5. J. Neuroimmunol. 189 23– 30. 10.1016/j.jneuroim.2007.06.011 17628702 · DOI
  149. Tison F. Keywood C. Wakefield M. Durif F. Corvol J. C. Eggert K. (2016). A phase 2A trial of the novel mGluR5-negative allosteric modulator dipraglurant for levodopa-induced dyskinesia in parkinson’s disease. Mov. Disord. 31 1373– 1380. 10.1002/mds.26659 27214664 · DOI
  150. Tomimoto H. Akiguchi I. Wakita H. Kimura J. (1997). [White matter lesions after occlusion of the bilateral carotid arteries in the rat–temporal profile of cerebral blood flow (CBF), oligodendroglia and myelin]. No To Shinkei 49 639– 644. 9234252
  151. Ullian E. M. Sapperstein S. K. Christopherson K. S. Barres B. A. (2001). Control of synapse number by glia. Science 291 657– 661. 10.1126/science.291.5504.657 11158678 · DOI · Paper page
  152. Vafabakhsh R. Levitz J. Isacoff E. Y. (2015). Conformational dynamics of a class C G-protein-coupled receptor. Nature 524 497– 501. 10.1038/nature14679 26258295 PMC4597782 · DOI
  153. Verderio C. (2013). Extracellular membrane microvesicles and nanotubes in the brain: understanding their nature, their function in cell-to-cell communication, their role in transcellular spreading of pathological agents and their therapeutic potential. Front. Physiol. 4: 163. 10.3389/fphys.2013.00163 23847543 PMC3696833 · DOI
  154. Verite J. Janet T. Chassaing D. Fauconneau B. Rabeony H. Page G. (2018). Longitudinal chemokine profile expression in a blood-brain barrier model from Alzheimer transgenic versus wild-type mice. J. Neuroinflammation 15: 182. 10.1186/s12974-018-1220-7 29898739 PMC6001165 · DOI
  155. Vermeiren C. Hemptinne I. Vanhoutte N. Tilleux S. Maloteaux J. M. Hermans E. (2006). Loss of metabotropic glutamate receptor-mediated regulation of glutamate transport in chemically activated astrocytes in a rat model of amyotrophic lateral sclerosis. J. Neurochem. 96 719– 731. 10.1111/j.1471-4159.2005.03577.x 16371010 · DOI
  156. Vermeiren C. Najimi M. Vanhoutte N. Tilleux S. de Hemptinne I. Maloteaux J. M. (2005). Acute up-regulation of glutamate uptake mediated by mGluR5a in reactive astrocytes. J. Neurochem. 94 405– 416. 10.1111/j.1471-4159.2005.03216.x 15998291 · DOI
  157. Vernon A. C. Smith E. J. Stevanato L. Modo M. (2011). Selective activation of metabotropic glutamate receptor 7 induces inhibition of cellular proliferation and promotes astrocyte differentiation of ventral mesencephalon human neural stem/progenitor cells. Neurochem. Int. 59 421– 431. 10.1016/j.neuint.2011.04.001 21624409 · DOI
  158. Wang J. W. Wang H. D. Cong Z. X. Zhang X. S. Zhou X. M. Zhang D. D. (2013). Activation of metabotropic glutamate receptor 5 reduces the secondary brain injury after traumatic brain injury in rats. Biochem. Biophys. Res. Commun. 430 1016– 1021. 10.1016/j.bbrc.2012.12.046 23261470 · DOI
  159. Werner P. Pitt D. Raine C. S. (2001). Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann. Neurol. 50 169– 180. 10.1002/ana.1077 11506399 · DOI
  160. Wilkinson B. L. Landreth G. E. (2006). The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer’s disease. J. Neuroinflammation 3: 30. 10.1186/1742-2094-3-30 17094809 PMC1637099 · DOI
  161. Xue F. Stoica B. A. Hanscom M. Kabadi S. V. Faden A. I. (2014). Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGluR5) attenuate microglial activation. CNS Neurol. Disord. Drug Targets 13 558– 566. 10.2174/18715273113126660199 24168364 · DOI
  162. Yang L. Mao L. Chen H. Catavsan M. Kozinn J. Arora A. (2006). A signaling mechanism from G alpha q-protein-coupled metabotropic glutamate receptors to gene expression: role of the c-Jun N-terminal kinase pathway. J. Neurosci. 26 971– 980. 10.1523/JNEUROSCI.4423-05.2006 16421317 PMC6675367 · DOI
  163. Yang P. Zhang J. Zhao L. Jiao Q. Jin H. Xiao X. (2012). Developmental distribution pattern of metabotropic glutamate receptor 5 in prenatal human hippocampus. Neurosci. Bull. 28 704– 714. 10.1007/s12264-012-1286-7 23225313 PMC5561823 · DOI
  164. Yao H. H. Ding J. H. Zhou F. Wang F. Hu L. F. Sun T. (2005). Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes. J. Neurochem. 92 948– 961. 10.1111/j.1471-4159.2004.02937.x 15686497 · DOI
  165. Ye X. Yu L. Zuo D. Zhang L. Zu J. Hu J. (2017). Activated mGluR5 protects BV2 cells against OGD/R induced cytotoxicity by modulating BDNF-TrkB pathway. Neurosci. Lett. 654 70– 79. 10.1016/j.neulet.2017.06.029 28642149 · DOI
  166. Yin S. Noetzel M. J. Johnson K. A. Zamorano R. Jalan-Sakrikar N. Gregory K. J. (2014). Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS. J. Neurosci. 34 79– 94. 10.1523/JNEUROSCI.1129-13.2014 24381270 PMC3866496 · DOI
  167. Zabel M. K. Kirsch W. M. (2013). From development to dysfunction: microglia and the complement cascade in CNS homeostasis. Ageing Res. Rev. 12 749– 756. 10.1016/j.arr.2013.02.001 23419464 PMC3700678 · DOI
  168. Zhang Z. Ma W. Wang L. Gong H. Tian Y. Zhang J. (2015). Activation of type 4 metabotropic glutamate receptor attenuates oxidative stress-induced death of neural stem cells with inhibition of JNK and p38 MAPK signaling. Stem Cells Dev. 24 2709– 2722. 10.1089/scd.2015.0067 26176363 PMC4652160 · DOI
  169. Zhao Z. Nelson A. R. Betsholtz C. Zlokovic B. V. (2015). Establishment and dysfunction of the blood-brain barrier. Cell 163 1064– 1078. 10.1016/j.cell.2015.10.067 26590417 PMC4655822 · DOI · Paper page
  170. Zhou F. Yao H. H. Wu J. Y. Yang Y. J. Ding J. H. Zhang J. (2006). Activation of Group II/III metabotropic glutamate receptors attenuates LPS-induced astroglial neurotoxicity via promoting glutamate uptake. J. Neurosci. Res. 84 268– 277. 10.1002/jnr.20897 16752416 · DOI
  171. Zipfel G. J. Babcock D. J. Lee J. M. Choi D. W. (2000). Neuronal apoptosis after CNS injury: the roles of glutamate and calcium. J. Neurotrauma 17 857– 869. 10.1089/neu.2000.17.857 11063053 · DOI

Cited by

Sorted by citations

Authors
Spampinato, S. F., Copani, A., Nicoletti, F., Sortino, M. A., & Caraci, F.
Affiliations
  • University of Catania (IT)
  • Istituto Neurologico Mediterraneo (IT)
Corresponding author
Caraci, Filippo
ORCID
Venue
Frontiers in Molecular Neuroscience
Publisher
Frontiers Media SA
Published
2018-11-13
Volume
11
Pages
414-414
ISSN
1662-5099 (ISSN-L)
DOI
10.3389/fnmol.2018.00414
PMC
PMC6243036
OpenAlex
W2898331726
Cited by
105
References
8
Citations by year
2026: 4 · 2025: 13 · 2024: 7 · 2023: 16 · 2022: 19 · 2021: 21 · 2020: 17 · 2019: 8
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
Ministero della Salute
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
metabotropic glutamate receptors, glial cells, neuroprotection, neurodegenerative diseases, astrocytes, microglia, oligodendrocytes, neuroinflammation, excitotoxicity, multiple sclerosis, glutamatergic neurotransmission, subtype-selective ligands

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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