title: NMDA-induced increases in rat brain glutamine synthetase but not glial fibrillary acidic protein are mediated by free radicals.
abstract: Both excitotoxicity and oxidative stress are implicated in the pathophysiology of central nervous system (CNS) ischaemia-reperfusion injury whereby astrocytes offer neural protection through the production of endogenous antioxidants and removal of glutamate from the extracellular milieu. This study investigated whether exogenous alpha-tocopherol, an antioxidant, could prevent N-methyl-D-aspartate (NMDA)-produced increases of the glial specific proteins, glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP) in rat brain spheroids in vitro. NMDA (320 microM; 3 days in vitro (DIV)) was unable to induce lipid peroxidation in rat brain spheroids implying that excitotoxicity in this system did not involve substantial free radical formation. However at non-cytotoxic concentrations, increases in astroglial GS were prevented by alpha-tocopherol treatment, suggesting a role for ROS in the excitotoxic process. In contrast, NMDA-induced increases in GFAP remained unchanged by alpha-tocopherol indicating that oxidative stress may not be involved in reactive gliosis at non-cytotoxic NMDA concentrations.
authors.affiliation: Department of Biosciences, University of Hertfordshire, Hatfield, UK. j.e.davenportjones@herts.ac.uk
authors.forename: J E
authors.initials: JE
authors.lastname: Davenport Jones
authors.forename: R M
authors.initials: RM
authors.lastname: Fox
authors.forename: C K
authors.initials: CK
authors.lastname: Atterwill
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D005609:Free Radicals / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D018874:Spheroids, Cellular; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D005609:Free Radicals; D005904:Glial Fibrillary Acidic Protein; D014810:Vitamin E; D016202:N-Methylaspartate; D005974:Glutamate-Ammonia Ligase