title: Metabotropic Glutamate Receptors Protect Oligodendrocytes from Acute Ischemia in the Mouse Optic Nerve.
abstract: Studies by Bruce Ransom and colleagues have made a major contribution to show that white matter is susceptible to ischemia/hypoxia. White matter contains axons and the glia that support them, notably myelinating oligodendrocytes, which are highly vulnerable to ischemic-hypoxic damage. Previous studies have shown that metabotropic GluRs (mGluRs) are cytoprotective for oligodendrocyte precursor cells and immature oligodendrocytes, but their potential role in adult white matter was unresolved. Here, we report that group 1 mGluR1/5 and group 2 mGluR3 subunits are expressed in optic nerves from mice aged postnatal day (P)8-12 and P30-35. We demonstrate that activation of group 1 mGluR protects oligodendrocytes against oxygen-glucose deprivation (OGD) in developing and young adult optic nerves. In contrast, group 2 mGluR are shown to be protective for oligodendrocytes against OGD in postnatal but not young adult optic nerves. The cytoprotective effect of group 1 mGluR requires activation of PKC, whilst group 2 mGluR are dependent on negatively regulating adenylyl cyclase and cAMP. Our results identify a role for mGluR in limiting injury of oligodendrocytes in developing and young adult white matter, which may be useful for protecting oligodendrocytes in neuropathologies involving excitoxicity and ischemia/hypoxia.
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK. arthur.butt@port.ac.uk.
authors.forename: Arthur M
authors.identifier: http://orcid.org/0000-0001-7579-0746
authors.initials: AM
authors.lastname: Butt
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vanzulli
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Papanikolaou
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
authors.forename: Irene Chacon
authors.initials: IC
authors.lastname: De La Rocha
authors.affiliation: Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK. virginia.hawkins@uconn.edu.|Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, 06269, USA. virginia.hawkins@uconn.edu.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D000242:Cyclic AMP; D005947:Glucose
keywords: Glutamate; Hypoxia; Ischemia; Metabotropic glutamate receptor; Oligodendrocyte; Optic nerve; White matter