An acute dysfunction of the glutamate transport activity has been shown to generate free radicals and suppress the anti-oxidant ability in the hippocampus of rats.
In this study, we attempted to elucidate whether or not an acute inhibition of glutamate transports activity with l-trans-pyrrolidine-2,4-dicarboxylic acid (l-trans PDC) would cause neuroexcitoxicity in the hippocampus. We used in vivo microdialysis and X-band electron spin resonance (ESR) spectroscopy to measure the changes in the redox state during the perfusion of l-trans PDC. ESR signals from rats using l-trans PDC were characteristically a six-line spectra, for which the hfc was a(N)=1.57mT and a(H)=0.25mT; these hfc's were obtained from the lipoxygenase/linoleic acid system that was used for the generation of lipid radicals. The antioxidant effect was measured using an ESR analysis to monitor sequential changes in the signal amplitude of nitroxide radical in the dialysate of both l-trans PDC and control animals. The pattern showed exponential decay with median half-life of the nitroxide radical took significantly longer in the l-trans PDC group. Acute changes in the glutamate transport resulted in the generation of a lipid radical and a depletion in the anti-oxidant effect in the hippocampus. Our data indicate that a dysfunction of a glutamate transport resulted in the collapse of the redox state, which thus eventually led to neuronal necrosis in the hippocampus. This study provides clear evidence for the mechanisms associated with neuronal disorder in relation to glutamate.
Nagatomo
Keiko
K
Section of Psychiatry, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Japan.
Ueda
Yuto
Y
Doi
Taku
T
Nakajima
Akira
A
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008055:Lipids; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019097:Spin Trapping
D027322:Amino Acid Transport System X-AG; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D008055:Lipids; D009498:Neurotoxins; D011759:Pyrrolidines; C103758:pyrrolidine-2,3-dicarboxylic acid; D018698:Glutamic Acid