The Neurotoxic Effect Of Organotin On Sebastiscus Marmoratus And Potential Mechanism

This study was conducted to investigate neurotoxic effect of Trimethyltin(TMT) and Tributyltin(TBT) on the neural system of Sebastiscus marmoratus.The potential mechanisms were studied after acute(5,50,500μg/kg) and chronic(10,100,1000 ng/L) exposure to organotin compounds,and the behavioral,histological, biochemical and molecular parameters were analyzed.1.The neurotoxic effect of acute administration of TMT on Sebastiscus marmoratus.After TMT exposure,the total tin in the brain was significantly increased in a dose-dependent manner.There was a significant increase in apoptotic cells in brain judged by TUNEL-positive cell after exposure to TMT,and the increase was in a dose-dependent manner.ROS,NO,NOS and Caspase-3 were analyzed after TMT exposure,the content of ROS and NO was significantly increased, the activities of NOS and Caspase-3 were increased and the activity of EROD was significantly decreased.These suggest that the oxidative stress should be one of mechanisms on the apoptosis induced by TMT.2.The neurotoxic effect and potential mechanisms of chronic TMT and TBT exposure on Sebastiscus marmoratus.The amino acid neurotransmitters and monoamine neurotransmitters were analyzed by HPLC.The results showed that the content of dopamine was significantly increased in a dose-dependent manner,NE, 5-HT and Glu were decreased in a dose-dependent manner after TMT and TBT exposure.The expression of neurotransmitter receptors and signal pathway factors were analyzed by Real-Time PCR.The expression of dopamine receptors(DR1 and DR2) and Glu receptors(NMDAR and AMPAR) were significantly decreased,the expression of CaM,CaMKII and CREB were also affected.These suggest that the disturbance of neurotransmitter,the alternation of neurotransmitter receptors and signal pathway were potential mechanism of neurotoxicity of TMT.