Excitotoxicity in Rat’s Brain Induced by Exposure of Manganese and Neuroprotective Effects of Pinacidil and Nimodipine

摘要

Manganese (Mn) is an essential trace element for humans. However, manganism would be caused by excessive Mn. The mechanisms underlying excitotoxicity induced by manganism are poorly understood. As it is known to us, glutamate (Glu) is the most prevalent excitatory neurotransmitter. To determine the possible role of dysfunction of Glu transportation and metabolism in Mn-induced excitotoxicity, the rats were ip injected with different dose of MnCl2 (0, 50, 100, and 200 μmol/kg), the levels of Mn and activities of GS, PAG, Na+-K+-ATPase, and Ca2+-ATPase in striatum were investigated. In addition, effect of 20.38 μmol/kg pinacidil (K+ channel opener) or 2.4 μmol/kg nimodipine (Ca2+ channel blocker) were studied at 200 μmol/kg MnCl2. With dose-dependent inhibition of GS, Na+-K+-ATPase, and Ca2+-ATPase activities, increase of Mn levels and PAG activity were observed. Further investigation indicated that pre-treatment of pinacidil or nimodipine reversed toxic effect of MnCl2 significantly. These results suggested that MnCl2 could induce dysfunction of Glu transportation and metabolism by augmenting the excitotoxicity dose-dependently; pinacidil and nimodipine might antagonize manganese neurotoxicity.