Krüger Katharina, Repges Hendrik, Hippler Jörg, Hartmann Louise M, Hirner Alfred V, Straub Heidrun, Binding Norbert, Musshoff Ulrich
Institut für Physiologie I, Universitätsklinikum Münster, Robert-Koch-Strasse 27a, D-48149 Münster, Germany.
Toxicol Appl Pharmacol. 2007 Nov 15;225(1):40-6. doi: 10.1016/j.taap.2007.07.007. Epub 2007 Jul 25.
In this study, the effects of pentavalent dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and trivalent dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 micromol/l. DMA(V) had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA(III) significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 micromol/l DMA(III) in adult and 10 micromol/l DMA(III) in young rats. Moreover, DMA(III) significantly affected the LTP-induction. Application of 10 micromol/l DMA(III) resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA(III). In slices of young rats, the depressant effects of DMA(III) were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA(V) on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential.
在本研究中,测试了五价二甲基胂酸((CH(3))(2)AsO(OH);DMA(V))和三价二甲基亚胂酸((CH(3))(2)As(OH);DMA(III))对幼年(14 - 21日龄)和成年(2 - 4月龄)大鼠海马切片中兴奋性谢弗侧支 - CA1突触产生的突触传递的影响。两种化合物均以1至100微摩尔/升的浓度施用。DMA(V)对成年或幼年大鼠CA1树突区域记录的诱发场兴奋性突触后电位(fEPSP)的幅度或长时程增强(LTP)的诱导均无影响。然而,DMA(III)的施用显著降低了诱发fEPSP的幅度,且呈浓度依赖性,在成年大鼠中施用100微摩尔/升DMA(III)以及在幼年大鼠中施用10微摩尔/升DMA(III)后会出现完全抑制。此外,DMA(III)显著影响LTP的诱导。施用10微摩尔/升DMA(III)导致成年和幼年大鼠切片中fEPSP幅度的突触后电位完全丧失。在对DMA(III)进行30分钟洗脱后,抑制作用不可逆。在幼年大鼠的切片中,DMA(III)的抑制作用比成年大鼠的切片更明显。与DMA(V)对突触传递(无)影响相比,三价化合物具有相当高的神经毒性潜力。