Experimental Study On The Effect Of AsHC 360 On LTP In Schaffer-CA1 Region Of Rat Hippocampus

Arsenolipids-AsHC 360 is a new type of arsenic containing hydrocarbons（AsHCs）detected in seafood in recent years.Its toxicological effects on human health have attracted more and more attention,including the effects on learning and memory at the developmental stage,but there is no research report.Long term potentiation（LTP）is regarded as a classic model for studying learning and memory.In this paper,the field excitatory postsynaptic potential（f EPSP）of Schaffer collateral CA1 field in hippocampus was recorded by using multi electrode array（MEA）system.The effects of AsHC 360 on LTP were analyzed by inductively coupled plasma mass spectrometer（ICPMS）.Firstly,after LTP was induced by 100 Hz high frequency stimulation（HFS）,1.5,3.75,7.5,15,45,150μg As L^-1AsHC 360 was introduced into the artificial cerebrospinal fluid to explore the effect of different concentrations of AsHC 360 on the maintenance period of LTP.The results showed that low concentration(1.5μg As L^-1)AsHC 360 had no effect on LTP maintenance period,while high concentration(45,150μg As L^-1)AsHC 360 inhibited LTP maintenance period;when the medium concentration(3.75,7.5,15μg As L^-1)AsHC 360 was perfused,the amplitude of f EPSP increased in varying degrees during the maintenance period of LTP,and the enhancement effect of 15μg As L^-1was the most obvious.In order to reveal the effect of AsHC 360 on LTP maintenance,ICPMS was used to analyze the relative changes of Na,K,Ca,Mg,Mn,Cu,Zn and As concentrations in hippocampal slices after electrophysiological experiments.It was found that Ca²⁺content in brain slices perfused with 15μg As L^-1AsHC 360 was significantly increased.It is speculated that Ca²⁺may be the key factor for 15μg As L^-1AsHC 360 to enhance the maintenance period of LTP.The gradient experiments with different extracellular Ca²⁺concentrations were designed.The results showed that 15μg As L^-1AsHC 360 could enhance the maintenance period of LTP by promoting the influx of Ca²⁺.Finally,in order to further explore the enhancement effect of AsHC 360 on LTP,1.5 and 15μg As L^-1AsHC 360 were infused 10 minutes before LTP induction by HFS.The results showed that 1.5 and 15μg As L^-1AsHC 360 had no effect on LTP induction period,but 15μg As L^-1AsHC 360 had no effect on LTP induction period.But the amplitude of f EPSP increased steadily after 15μg As L^-1AsHC 360 perfusion,which proved that the effect of AsHC 360 on LTP was in the maintenance period rather than in the induction period.In conclusion,from the perspective of electrophysiological experiments of hippocampal slices in vitro,this paper explored the regulation of different concentrations of AsHC 360 on LTP maintenance period and induction period,and proposed that 15μg As L^-1AsHC 360 may enhance the maintenance period of LTP by promoting Ca²⁺influx.The results of this study provide experimental support for determining the neurotoxic effect of AsHCs on synaptic plasticity LTP,and provide a new idea for further study of the molecular regulatory mechanism of AsHCs on learning and memory.