NMDA-induced increases in rat brain glutamine synthetase but not glial fibrillary acidic protein are mediated by free radicals.
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.
Davenport Jones
J E
JE
Department of Biosciences, University of Hertfordshire, Hatfield, UK. j.e.davenportjones@herts.ac.uk
Fox
R M
RM
Atterwill
C K
CK
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
D005609:Free Radicals; D005904:Glial Fibrillary Acidic Protein; D014810:Vitamin E; D016202:N-Methylaspartate; D005974:Glutamate-Ammonia Ligase