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- Title
INVOLVEMENT OF GLUTAMINE SYNTHETASE IN KAINIC ACID MEDIATED EXCITOTOXICITY IN RAT BRAIN.
- Authors
Swamy, M.; Sirajudeen, K. N. S.; Govindasamy, Chandran
- Abstract
Introduction: Glutamate is considered highly neurotoxic when accumulated in massive amounts in the extra cellular space in brain. Neuronal excitation involving the excitatory glutamate receptors is recognized as an important underlying mechanism in neurodegenerative disorders. In the central nervous system, the conversion of glutamate to glutamine that takes place within the astrocytes represents a key mechanism in the regulation of excitatory neurotransmission under normal conditions as well as in injured brain. It is reported that glutamine synthetase activity is decreased by nitric oxide (NO) in rat brain in ammonia toxicity. To understand the modulation of glutamine synthetase activity by NO in excitotoxicity, nitrate /nitrite (NOx) and glutamine synthetase were analyzed in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to excitotoxicity by kainic acid. Methodology: Excitotoxicity was produced in adult male Sprague-Dawley rats by subcutaneous administration of kainic acid (15mg/kg body weight, dissolved in normal saline). Control rats received normal saline. The animals were sacrificed after 2 hours of injection and brain regions (CC, CB and BS) were separated and homogenized. In the homogenates, the NO was estimated as Nitrate/Nitrite and the activity of glutamine synthetase was assayed by colorimetric method. Statistical analysis of results was done by using independent student t-test. Results: The concentration of NOx was increased (p < 0.001 in CC, CB and p< 0.01 in BS) and glutamine synthetase activity was decreased (p<0.001 in CC, CB & BS) in kainic acid mediated excitotoxicity. Conclusions: The results of this study clearly demonstrated the increased formation of NO and suggest the involvement of NO in the pathophysiology of excitotoxicity. The decreased activity of glutamine synthetase indicates the modulation of its activity by NO. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid for excitotoxicity leading to neuronal damage.
- Publication
Malaysian Journal of Medical Sciences, 2007, Vol 14, p111
- ISSN
1394-195X
- Publication type
Academic Journal