1. The protective effect of riluzole on manganese caused disruption of glutamate-glutamine cycle in rats.
- Author
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Deng Y, Xu Z, Xu B, Tian Y, Xin X, Deng X, and Gao J
- Subjects
- Animals, Blotting, Western, Corpus Striatum chemistry, Corpus Striatum drug effects, Corpus Striatum enzymology, Excitatory Amino Acid Transporter 1 metabolism, Excitatory Amino Acid Transporter 2 metabolism, Female, Glutamate-Ammonia Ligase metabolism, Glutaminase metabolism, Male, Manganese metabolism, Manganese Compounds, Manganese Poisoning metabolism, Neuroprotective Agents metabolism, Neuroprotective Agents pharmacology, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Riluzole metabolism, Sodium-Potassium-Exchanging ATPase metabolism, Chlorides toxicity, Corpus Striatum metabolism, Glutamic Acid metabolism, Glutamine metabolism, Riluzole pharmacology
- Abstract
The mechanisms underlying the disruption of glutamate-glutamine cycle (Glu-Gln cycle) in manganism are still unknown. To approach the concrete mechanisms, the rats were i.p. injected with different doses of MnCl(2) (0, 8, 40, and 200 micromol/kg), and the levels of Mn, Glu, and Gln, the morphological and ultrastructural changes, activities of Na(+)-K(+)-ATPase, GS, and PAG, mRNA and protein expression of GS, GLAST, and GLT-1 in the striatum were investigated. In addition, the effect of 21.35 micromol/kg riluzole (Na(+) channel blocker) was studied at 200 micromol/kg MnCl(2). It was observed that (1) Mn and Glu levels and PAG activity increased; (2) many pathological changes occurred; (3) Gln levels, Na(+)-K(+)-ATPase and GS activities, and GS, GLAST, and GLT-1 mRNA and protein expression inhibited, does dependently. Furthermore, the research indicated that pretreatment of riluzole reversed toxic effects of MnCl(2) significantly. These results suggested that Glu-Gln cycle was disrupted by Mn exposure dose dependently; riluzole might antagonize Mn neurotoxicity.
- Published
- 2009
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