NMDA Receptor Activation Alters Redox in the Hippocampus.
Abstract number :
1.016
Submission category :
Year :
2001
Submission ID :
256
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
R. Takeda, Dr, Psychiatry, Miyazaki Medical College, Miyazaki, Japan; Y. Ueda, Dr, Psychiatry, Miyazaki Medical College, Miyazaki, Japan; T. Doi, Dr, Psychiatry, Miyazaki Medical College, Miyazaki, Japan; J. Tokumaru, Dr, Psychiatry, Miyazaki Medical Coll
RATIONALE: It has been shown by in vitro studies that glutamate-induced neuroexcitotoxicity can be caused by reactive oxygen species or by free radical generation followed by glutamate receptor activation. However, there are few studies of the condition of electron paramagnetism resonance (EPR) in living animals. To study redox in living animals we used in vivo microdialysis with EPR spectroscopy to examine the changes in redox state during perfusion of the hippocampus with NMDA in freely moving animals.
METHODS: Following anesthesia with pentobarbital (37.5 mg per kg i.p.) male Wistar rats were stereotaxically implanted in ventral hippocampus with a microdialysis probe. After recovery, the microdialysis outlet was connected to an EPR resonator. Freely moving rats underwent hippocampal perfusion at 2 ul per min for 40 min with 0.1mM NMDA. Free radicals were detected using the spin trap POBN. Antioxidant ability was examined utilizing the principle that exogenously applied nitroxide radicals (carbamoyl-PROXYL) reduced paramagnetism in the brain, and the decay rate of ESR signal intensities would reflect the antioxidant ability (i.e. half-life).
RESULTS: Control rats did not form a POBN adduct. However, perfusion with NMDA caused an ESR spectra with hfc of: aN=15.7G and aH=2.5G, corresponding to a lipoxygenase-linoleic acid generated lipid radical. Median half-life of the nitroxide radical was significantly longer in the NMDA group than in control.
CONCLUSIONS: With epileptogenesis, the NMDA receptor is thought to be important in excitatory neurotransmission and neurodegeneration in the hippocampus. In our study, activation of receptors by NMDA resulted in the generation of lipid radicals and reduced antioxidant ability in the hippocampus. These results show direct EPR evidence that activation of NMDA also is associated with collapse of redox state as well. We wonder if regulation of NMDA receptor activation is an indirect effect of epileptogenesis since lipid peroxidation seems common to many effects in hippocampus rather than unique to specific models such as electrical kindling.
Support: This study was partially supported by a Grant-in-Aid for Encouragement of Young Scientists (12770537) from the Ministry of Education, Science, Sport and Culture, Japan. (to Y.U.)