慢性应激所致大鼠海马长时程增强和氨基酸类神经递质的改变及苯妥英钠的效应(英文)

Effects of phenytoin on the changes of long-term potentiation and amino acid neurotransmitters in rat hippocampus induced by chronic stress

目的探讨慢性应激对大鼠海马长时程增强 (LTP)和氨基酸类神经递质的影响及苯妥英钠对它们的效应。方法将 2 4只SD雄性大鼠随机分为对照组、应激 +生理盐水组和应激 +苯妥英钠组 ,每组 8只。采用离体海马脑片结合电生理的方法观测海马CA1区LTP的变化。以群体峰电位 (PS)的幅值和场兴奋性突触后电位 (fEPSP)的斜率作为观察LTP变化的指标。应用高效液相色谱紫外检测法检测海马氨基酸类神经递质的含量。结果 (1)应激 +生理盐水组PS幅值和fEPSP斜率在高频串刺激后增大的幅度低于对照组和应激 +苯妥英钠组 (P <0 .0 5 )。 (2 )应激 +生理盐水组和应激+苯妥英钠组的天冬氨酸含量 [分别为 (4 .746± 0 .60 9) μmol/g和 (4 .948± 0 .75 1) μmol/ g]高于对照组 [(2 .42 5± 0 .2 11)μmol/ g ,P <0 .0 1] ;应激 +生理盐水组的谷氨酸含量 [(8.0 94± 1.0 3 5 ) μmol/ g]高于对照组 [(6.0 16± 0 .677) μmol/g]和应激 +苯妥英钠组 [(6.970± 0 .64 7) μmol/g] ;P <0 .0 5 ;应激 +苯妥英钠组的GABA含量 [(5 .14 2± 0 .662 ) μmol/g]高于对照组 [(4 .2 2 9± 0 .44 9) μmol/ g]和应激 +生理盐水组 [(4 .2 49± 0 .463 ) μmol/g] ,P <0 .0 1。结论慢性应激使大鼠海马CA1区LTP的形成受抑制 ,天冬氨酸和谷氨酸?

Background Chronic stress involves in many mental and physical disorders, while its pathogenesis has not been fully elucidated. We investigated the changes of long-term potentiation and amino acid neurotransmitters in rat hippocampus induced by chronic stress and the effects of phenytoin on them. MethodsIsolated hippocampal slices of rats were used to observe the changes of long term potentiation (LTP) in hippocampal CA1 field using electrophysiological technique.Amplitude of population spike (PS) and field excitatory postsynaptic potentials (fEPSPs) slope were used to indicate the changes of LTP. High frequency stimulation (HFS) was applied to Schaffer collaterals of hippocampal CA3 field, and the changes of PS amplitude and fEPSPs slope in CA1 field were observed. High performance liquid chromatography (HPLC) coupled with UV detection was used for quantification of hippocampal amino acids. ResultsThe increases of PS amplitude and fEPSPs slope after HFS in control and stress phenytoin groups were significantly greater than those in stress saline group (P<0.05).The levels of aspartate in control group were significantly lower than those in stress saline and stress phenytoin groups(P<0.01);glutamate in control and stress phenytoin groups were significantly lower than those in stress saline group(P<0.05);γ aminobutyric acid(GABA) in stress phenytoin groups was significantly higher than those in control and stress saline groups(P<0.01). ConclusionsStress could suppress the development of LTP in hippocampal CA1 field and increase the levels of hippocampal aspartate and glutamate, but not the level of GABA. Phenytoin could keep LTP normal in stressed hippocampus, which may be involved in reducing glutamate and increasing GABA.