Neurophysiologic effects of folate compounds in hippocampus, in vitro.
Neurophysiologic effects of folate compounds in hippocampus, in vitro.
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叶酸化合物在体外对海马的神经生理作用。
DOI：
10.1016/0006-8993(83)90651-0
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发表时间：
1983
期刊：
影响因子：
2.9
通讯作者：
Ferrendelli,JA
中科院分区：
文献类型：
--
作者：
Clifford,DB;Ferrendelli,JA
本文研究了蝶酰谷氨酸（PGA，叶酸）及其有关化合物对离体豚鼠海马脑片的电生理作用。叶酸被发现在CA 3中具有显著的神经兴奋作用，在CA 1中具有较小但实质性的兴奋作用。叶酸对齿状回的激活作用最小。CA 3中的细胞外记录显示单个单位活动、诱发反应增强，并且在50-100 μM PGA浓度下，产生自发性癫痫样放电。PGA浓度逐渐增加至至少2 mM不会导致该活性丧失。在200 μM的浓度下，CA 3中的癫痫样爆发先于CA 1中的癫痫样爆发，CA 1中的癫痫样爆发因切断Schaeffer侧支通路而消失。然而，在500 μM PGA的情况下，在从CA 3分离的CA 1中发生自发爆发。PGA引起的变化主要影响群体峰电位，导致刺激阈值降低和幅度反应升高，测定叶酸类化合物产生自发性癫痫样活动所需的阈浓度，其效力顺序为：蝶酰谷氨酸（PGA）≥甲酰四氢叶酸（亚叶酸）> >甲基四氢叶酸（MTHF）≥甲氨蝶呤（MTX）≥谷氨酸。蝶酸、蝶呤、N（对氨基苯甲酰基）L-谷氨酸无活性。甲氨蝶呤不会降低对PGA的反应。因此，需要整个叶酸分子才能充分发挥活性。叶酸代表天然存在的高度致癫痫化合物，其作用机制不依赖于代谢产物。可能它们作为神经调质作用于中枢受体。
Pteroylglutamic acid (PGA, folic acid) and related compounds were studied for their electropysiologic effects on guinea pig hippocampal slices in vitro. Folates are found to have marked neuroexcitatory actions in CA3 and lesser but substantial excitatory effects in CA1. The dentate gyrus is minimally activated by folates. Extracellular recordings in CA3 reveal augmentation in single unit activity, evoked responses, and at 50–100 μM PGA concentrations, spontaneous epileptiform discharges are generated. Progressive increase in PGA concentrations to at least 2 mM do not result in loss of this activity. At concentrations of 200 μM, epileptiform bursts in CA3, precede those in CA1 which are lost by sectioning the Schaeffer collateral pathway. However, with 500 μM PGA, spontaneous bursts occur in CA1 isolated from CA3. The change induced by PGA primarily affects the population spike resulting in lower stimulus threshold and higher amplitude response.Measurement of threshold concentration necessary to produce spontaneous epileptiform activity of folate related compounds reveals the following order of potency: pteroylglutamic acid (PGA) ≥ formyl tetrahydrofolic acid (folinic acid) > > methyltetrahydrofolate (MTHF) ≥ methotrexate (MTX) ≥ glutamic acid. Pteroic acid, pterin,N(p-aminobenzoyl)L-glutamic acid are inactive. Methotrexate does not diminish the response to PGA. Thus, the entire folate molecule is needed for full activity. Folates represent naturally occurring, highly epileptogenic compounds whose mechanism of action is not dependent on metabolic products. Possibly they act at a central receptor as a neuromodulator.