{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:20:08Z","timestamp":1774020008333,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Physics and Mathematics (project \u201cArtificial intelligence and big data in technical, industrial, natural and social systems\u201d)"},{"name":"The Core Facilities \u201cMolecular Biology and Neurophysiology\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Brain hypoxia remains an Achilles\u2019 heel for public health that must be urgently addressed. Hypoxic damage affects both neurons and glial cells, particularly astrocytes, which are in close dynamic bi-directional communication, and are organized in plastic and tightly regulated networks. However, astroglial networks have received limited attention regarding their influence on the adaptive functional rearrangements of neural networks to oxygen deficiency. Herein, against the background of astrocytic Cx43 gap junction blockade by the selective blocker Gap19, we evaluated the features of spontaneous calcium activity and network characteristics of cells in primary cultures of the cerebral cortex, as well as the expression levels of metabotropic glutamate receptors 2 (mGluR2) and 5 (mGluR5) in the early and late periods after simulated hypoxia in vitro. We showed that, under normoxic conditions, blockade of Cx43 leads to an increase in the expression of metabotropic glutamate receptors mGluR2 and mGluR5 and long-term modulation of spontaneous calcium activity in primary cortical cultures, primarily expressed in the restructuring of the functional architectonics of neuron\u2013glial networks through reducing the level of correlation between cells in the network and the percentage of existing correlated connections between cells. Blocking Cx43 during hypoxic injury has a pronounced neuroprotective effect. Together with the increased expression of mGluR5 receptors, a decrease in mGluR2 expression to the physiological level was found, which suggests the triggering of alternative molecular mechanisms of cell adaptation to hypoxia. Importantly, the blockade of Cx43 in hypoxic damage contributed to the maintenance of both the main parameters of the spontaneous calcium activity of primary cortical cultures and the functional architectonics of neuron\u2013glial networks while maintaining the profile of calcium oscillations and calcium signal communications between cells at a highly correlated level. Our results demonstrate the crucial importance of astrocytic networks in functional brain adaptation to hypoxic damage and could be a promising target for the development of rational anti-hypoxic therapy.<\/jats:p>","DOI":"10.3390\/membranes12100948","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T22:53:19Z","timestamp":1664405599000},"page":"948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unravelling Contributions of Astrocytic Connexin 43 to the Functional Activity of Brain Neuron\u2013Glial Networks under Hypoxic State In Vitro"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-5035","authenticated-orcid":false,"given":"Tatiana A.","family":"Mishchenko","sequence":"first","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman S.","family":"Yarkov","sequence":"additional","affiliation":[{"name":"Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-470X","authenticated-orcid":false,"given":"Mariia O.","family":"Saviuk","sequence":"additional","affiliation":[{"name":"Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-5149","authenticated-orcid":false,"given":"Mikhail I.","family":"Krivonosov","sequence":"additional","affiliation":[{"name":"Institute of Information, Technology, Mathematics and Mechanics, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey D.","family":"Perenkov","sequence":"additional","affiliation":[{"name":"Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-6906","authenticated-orcid":false,"given":"Sergey V.","family":"Gudkov","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9759-6477","authenticated-orcid":false,"given":"Maria V.","family":"Vedunova","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2174\/1570161115666161104095522","article-title":"Apoptosis and Acute Brain Ischemia in Ischemic Stroke","volume":"15","author":"Radak","year":"2017","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22325","DOI":"10.1074\/jbc.M115.656405","article-title":"The Role of Mitochondrially Derived ATP in Synaptic Vesicle Recycling","volume":"290","author":"Pathak","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.cell.2013.12.042","article-title":"Activity-Driven Local ATP Synthesis Is Required for Synaptic Function","volume":"156","author":"Rangaraju","year":"2014","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1073\/pnas.1214912110","article-title":"Cortical Energy Demands of Signaling and Nonsignaling Components in Brain Are Conserved across Mammalian Species and Activity Levels","volume":"110","author":"Hyder","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.neuron.2012.08.019","article-title":"Synaptic Energy Use and Supply","volume":"75","author":"Harris","year":"2012","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"703084","DOI":"10.3389\/fcell.2021.703084","article-title":"Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease","volume":"9","author":"Mitroshina","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dom\u00e8nech, M., Hern\u00e1ndez, A., Plaja, A., Mart\u00ednez-Balibrea, E., and Bala\u00f1\u00e0, C. (2021). Hypoxia: The Cornerstone of Glioblastoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212608"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lest\u00f3n Pinilla, L., Ugun-Klusek, A., Rutella, S., and de Girolamo, L.A. (2021). Hypoxia Signaling in Parkinson\u2019s Disease: There Is Use in Asking \u201cWhat HIF?\u201d. Biology, 10.","DOI":"10.3390\/biology10080723"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"579953","DOI":"10.3389\/fnins.2020.579953","article-title":"Excitotoxicity: Still Hammering the Ischemic Brain in 2020","volume":"14","author":"Choi","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mukandala, G., Tynan, R., Lanigan, S., and O\u2019Connor, J.J. (2016). The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS. Brain Sci., 6.","DOI":"10.3390\/brainsci6010006"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neures.2017.11.013","article-title":"Astrocytes and Ischemic Tolerance","volume":"126","author":"Hirayama","year":"2018","journal-title":"Neurosci. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1152\/jn.00098.2017","article-title":"Loss and Recovery of Functional Connectivity in Cultured Cortical Networks Exposed to Hypoxia","volume":"118","author":"Erkamp","year":"2017","journal-title":"J. Neurophysiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Ortega, F. (2017). Neural Network Reconfigurations: Changes of the Respiratory Network by Hypoxia as an Example. The Plastic Brain, Springer.","DOI":"10.1007\/978-3-319-62817-2_12"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fncel.2017.00174","article-title":"Connexin-Dependent Neuroglial Networking as a New Therapeutic Target","volume":"11","author":"Naus","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.00042.2016","article-title":"Physiology of Astroglia","volume":"98","author":"Verkhratsky","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fncel.2015.00267","article-title":"Diseases Associated with Leaky Hemichannels","volume":"9","author":"Retamal","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1007\/s11064-017-2313-x","article-title":"Connexin Channels at the Glio-Vascular Interface: Gatekeepers of the Brain","volume":"42","author":"Leybaert","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1007\/s00429-017-1383-5","article-title":"Human Astrocytes: Structure and Functions in the Healthy Brain","volume":"222","author":"Vasile","year":"2017","journal-title":"Brain Struct. Funct."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/978-981-13-9913-8_11","article-title":"Astroglia in Alzheimer\u2019s Disease","volume":"1175","author":"Verkhratsky","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/jnr.24088","article-title":"Connexins and Pannexins: At the Junction of Neuro-Glial Homeostasis & Disease","volume":"96","author":"Lapato","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3389\/fneur.2020.00703","article-title":"The Multifaceted Role of Astrocyte Connexin 43 in Ischemic Stroke through Forming Hemichannels and Gap Junctions","volume":"11","author":"Liang","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s12079-017-0430-6","article-title":"Acute Connexin43 Temporal and Spatial Expression in Response to Ischemic Stroke","volume":"12","author":"She","year":"2018","journal-title":"J. Cell Commun. Signal"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2329048X1454495","DOI":"10.1177\/2329048X14544955","article-title":"Connexin 43 and Its Hemichannels Mediate Hypoxia\u2013Ischemia-Induced Cell Death in Neonatal Rats","volume":"1","author":"Wang","year":"2014","journal-title":"Child Neurol. Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.brainresbull.2018.12.009","article-title":"Inhibition of Connexin43 Hemichannels with Gap19 Protects Cerebral Ischemia\/Reperfusion Injury via the JAK2\/STAT3 Pathway in Mice","volume":"146","author":"Chen","year":"2019","journal-title":"Brain Res. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s12974-018-1230-5","article-title":"Astrocytic Gap Junction Inhibition by Carbenoxolone Enhances the Protective Effects of Ischemic Preconditioning Following Cerebral Ischemia","volume":"15","author":"Ma","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/NEN.0b013e3181cd44df","article-title":"The Connexin43 C-Terminal Region Mediates Neuroprotection during Stroke","volume":"69","author":"Kozoriz","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/glia.20926","article-title":"Hypoxia in High Glucose Followed by Reoxygenation in Normal Glucose Reduces the Viability of Cortical Astrocytes through Increased Permeability of Connexin 43 Hemichannels","volume":"58","author":"Orellana","year":"2010","journal-title":"Glia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mcn.2010.05.007","article-title":"Inhibition of Cytokine-Induced Connexin43 Hemichannel Activity in Astrocytes Is Neuroprotective","volume":"45","author":"Froger","year":"2010","journal-title":"Mol. Cell Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00232-007-9043-y","article-title":"Possible Involvement of Different Connexin43 Domains in Plasma Membrane Permeabilization Induced by Ischemia-Reperfusion","volume":"218","author":"Retamal","year":"2007","journal-title":"J. Membr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1016\/S0002-9440(10)63765-0","article-title":"Increased Apoptosis and Inflammation after Focal Brain Ischemia in Mice Lacking Connexin43 in Astrocytes","volume":"164","author":"Nakase","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fncel.2013.00149","article-title":"Seizure-like Activity in Hyaluronidase-Treated Dissociated Hippocampal Cultures","volume":"7","author":"Vedunova","year":"2013","journal-title":"Front. Cell Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Loginova, M., Mishchenko, T., Savyuk, M., Guseva, S., Gavrish, M., Krivonosov, M., Ivanchenko, M., Fedotova, J., and Vedunova, M. (2021). Double-Edged Sword of Vitamin D3 Effects on Primary Neuronal Cultures in Hypoxic States. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115417"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mitroshina, E.V., Loginova, M.M., Savyuk, M.O., Krivonosov, M.I., Mishchenko, T.A., Tarabykin, V.S., Ivanchenko, M.V., and Vedunova, M.V. (2021). Neuroprotective Effect of Kinase Inhibition in Ischemic Factor Modeling In Vitro. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041885"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.3389\/fphys.2018.01925","article-title":"Features of Neural Network Formation and Their Functions in Primary Hippocampal Cultures in the Context of Chronic TrkB Receptor System Influence","volume":"9","author":"Mishchenko","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_35","first-page":"6","article-title":"Morphofunctional Patterns of Neuronal Network Developing in Dissociated Hippocampal Cell Cultures","volume":"5","author":"Shirokova","year":"2013","journal-title":"Sovrem. Tehnol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"453901","DOI":"10.1155\/2015\/453901","article-title":"TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor","volume":"2015","author":"Vedunova","year":"2015","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Savyuk, M.O., Turubanova, V.D., Mishchenko, T.A., Lermontova, S.A., Klapshina, L.G., Krysko, D.V., and Vedunova, M.V. (2022). Unraveling of Functional Activity of Primary Hippocampal Neuron-Glial Networks in Photodynamic Therapy Based on Tetracyanotetra(Aryl)Porphyrazines. Cells, 11.","DOI":"10.3390\/cells11071212"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Savyuk, M., Krivonosov, M., Mishchenko, T., Gazaryan, I., Ivanchenko, M., Khristichenko, A., Poloznikov, A., Hushpulian, D., Nikulin, S., and Tonevitsky, E. (2020). Neuroprotective Effect of HIF Prolyl Hydroxylase Inhibition in an In Vitro Hypoxia Model. Antioxidants, 9.","DOI":"10.3390\/antiox9080662"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kustikova, V., Krivonosov, M., Pimashkin, A., Denisov, P., Zaikin, A., Ivanchenko, M., Meyerov, I., and Semyanov, A. (2018, January 5\u20137). CalciumCV: Computer Vision Software for Calcium Signaling in Astrocytes. Proceedings of the International Conference on Analysis of Images, Social Networks and Texts, Moscow, Russia. Lecture Notes in Computer Science (Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics).","DOI":"10.1007\/978-3-030-11027-7_17"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.3389\/fbioe.2022.895406","article-title":"3D-Printed Hyaluronic Acid Hydrogel Scaffolds Impregnated with Neurotrophic Factors (BDNF, GDNF) for Post-Traumatic Brain Tissue Reconstruction","volume":"10","author":"Mishchenko","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111801","DOI":"10.1016\/j.jep.2019.03.028","article-title":"Rhodiola Crenulata Attenuates Apoptosis and Mitochondrial Energy Metabolism Disorder in Rats with Hypobaric Hypoxia-Induced Brain Injury by Regulating the HIF-1\u03b1\/MicroRNA 210\/ISCU1\/2(COX10) Signaling Pathway","volume":"241","author":"Wang","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.brainres.2009.04.054","article-title":"Taurine Protects Transformed Rat Retinal Ganglion Cells from Hypoxia-Induced Apoptosis by Preventing Mitochondrial Dysfunction","volume":"1279","author":"Chen","year":"2009","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107066","DOI":"10.1016\/j.nlm.2019.107066","article-title":"Prenatal Hypoxia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats","volume":"164","author":"Zhuravin","year":"2019","journal-title":"Neurobiol. Learn Mem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1365-2990.1997.tb01181.x","article-title":"Apoptosis and Necrosis in the Newborn Piglet Brain Following Transient Cerebral Hypoxia-Ischaemia","volume":"23","author":"Yue","year":"1997","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrn3962","article-title":"From the Neuron Doctrine to Neural Networks","volume":"16","author":"Yuste","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mitroshina, E.V., Loginova, M.M., Yarkov, R.S., Urazov, M.D., Novozhilova, M.O., Krivonosov, M.I., Ivanchenko, M.V., and Vedunova, M.V. (2022). Inhibition of Neuronal Necroptosis Mediated by RIPK1 Provides Neuroprotective Effects on Hypoxia and Ischemia In Vitro and In Vivo. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020735"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mitroshina, E., Mishchenko, T., Usenko, A., Epifanova, E., Yarkov, R., Gavrish, M., Babaev, A., and Vedunova, M. (2018). AAV-Syn-BDNF-EGFP Virus Construct Exerts Neuroprotective Action on the Hippocampal Neural Network during Hypoxia In Vitro. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082295"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nrn1722","article-title":"Astrocytes, from Brain Glue to Communication Elements: The Revolution Continues","volume":"6","author":"Volterra","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/s41593-020-0679-6","article-title":"Astrocytes Contribute to Remote Memory Formation by Modulating Hippocampal-Cortical Communication during Learning","volume":"23","author":"Kol","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20130595","DOI":"10.1098\/rstb.2013.0595","article-title":"Astroglial Cradle in the Life of the Synapse","volume":"369","author":"Verkhratsky","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/jnr.10610","article-title":"Rapid Method for Culturing Embryonic Neuron-Glial Cell Cocultures","volume":"72","author":"Svenningsen","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2174\/157488908786242452","article-title":"Gap Junctions as Therapeutic Targets in Brain Injury Following Hypoxia-Ischemia","volume":"3","author":"Sahores","year":"2008","journal-title":"Recent Pat. CNS Drug Discov."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nrn1870","article-title":"Astrocyte Dysfunction in Neurological Disorders: A Molecular Perspective","volume":"7","author":"Seifert","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3389\/fncel.2018.00508","article-title":"Group II Metabotropic Glutamate Receptors Mediate Presynaptic Inhibition of Excitatory Transmission in Pyramidal Neurons of the Human Cerebral Cortex","volume":"12","author":"Bocchio","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1177\/1073858402238514","article-title":"Metabotropic Glutamate Receptors: Electrical and Chemical Signaling Properties","volume":"8","author":"Coutinho","year":"2002","journal-title":"Neuroscientist"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1523\/JNEUROSCI.3451-13.2014","article-title":"Intracellular MGluR5 Can Mediate Synaptic Plasticity in the Hippocampus","volume":"34","author":"Purgert","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fphar.2012.00199","article-title":"Translational Concepts of MGluR5 in Synaptic Diseases of the Brain","volume":"3","author":"Piers","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/aps.2009.24","article-title":"Molecular Mechanisms of Excitotoxicity and Their Relevance to Pathogenesis of Neurodegenerative Diseases","volume":"30","author":"Dong","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/glia.21086","article-title":"Neuroinflammation Is Associated with Changes in Glial MGluR5 Expression and the Development of Neonatal Excitotoxic Lesions","volume":"59","author":"Brownell","year":"2011","journal-title":"Glia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fnmol.2019.00020","article-title":"Role of Metabotropic Glutamate Receptors in Neurological Disorders","volume":"12","author":"Crupi","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.phrs.2016.11.013","article-title":"Metabotropic Glutamate Receptors and Neurodegenerative Diseases","volume":"115","author":"Ribeiro","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuroscience.2015.03.063","article-title":"Astrocytic MGluR5 and the Tripartite Synapse","volume":"323","author":"Panatier","year":"2016","journal-title":"Neuroscience"}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/12\/10\/948\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:41:25Z","timestamp":1760143285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/12\/10\/948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,28]]},"references-count":63,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["membranes12100948"],"URL":"https:\/\/doi.org\/10.3390\/membranes12100948","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,28]]}}}