The protective effect of riluzole on manganese caused disruption of glutamate-glutamine cycle in rats

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 MnCl2 (0, 8, 40, and 200 mu mol/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 mu mol/kg riluzole (Na+ channel blocker) was studied at 200 mu mol/kg MnCl2. 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 MnCl2 significantly. These results suggested that Glu-Gln cycle was disrupted by Mn exposure dose dependently; riluzole might antagonize Mn neurotoxicity. (C) 2009 Elsevier B.V. All rights reserved.