Proline-induced inhibition of glutamate release in hippocampal area CA1
Proline-induced inhibition of glutamate release in hippocampal area CA1
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DOI：
10.1016/s0006-8993(97)00721-x
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发表时间：
1997-09-26
期刊：
影响因子：
2.9
通讯作者：
Nadler, JV
中科院分区：
文献类型：
--
作者：
Cohen, SM;Nadler, JV
人类脑脊液中典型的脯氨酸浓度被证明增强了大鼠海马区CA1锥体细胞上Schaffer侧支-连合突触的传递。这项研究验证了这一假说，即脯氨酸通过增加谷氨酸的释放来增强兴奋性突触传递。使用两种浓度的Pro：一种是正常人脑脊液的典型浓度(3µM)，另一种是遗传性II型高脯氨酸血症患者脑脊液的典型浓度(30µM)。将海马片连续暴露于任一浓度的Pro可增强Schaffer侧支-连合突触传递。Pro使田间EPSP斜率与纤维截留幅度的关系曲线上移。与原假设相反的是，两种浓度的Pro都不会降低成对脉冲的易化作用；30mU的Pro能促进成对脉冲的易化，而3mU的Pro对成对的脉冲易化没有影响。与增强双脉冲易化作用相一致的是，30 mU M-Pro抑制了K+诱发的CA1脑片谷氨酸和天冬氨酸的释放以及4-氨基吡啶引起的CA1突触体内谷氨酸和天冬氨酸的释放。这些结果表明，Pro诱导的Schaffer侧支-连合突触传递的增强可能涉及突触后机制，而不是突触前机制。人体脑脊液中通常存在的脯氨酸浓度对谷氨酸的释放几乎没有影响。然而，脯氨酸诱导的谷氨酸释放抑制可能导致与II型高脯氨酸血症相关的神经精神障碍。(C)1997年埃尔塞维尔科学公司B.V.
Concentrations of proline typical of human CSF have been shown to potentiate transmission at Schaffer collateral-commissural synapses on CA1 pyramidal cells of the rat hippocampus. This study tested the hypothesis that proline enhances excitatory synaptic transmission by increasing glutamate release. Two concentrations of proline were used: a concentration typical of normal human CSF (3 mu M) and a concentration typical of CSF in persons with the genetic disorder hyperprolinemia type II (30 mu M). Continuous exposure of hippocampal slices to either concentration of proline potentiated Schaffer collateral-commissural synaptic transmission. Proline shifted the plot of field EPSP slope against fiber volley amplitude upward. Contrary to the original hypothesis, neither concentration of proline reduced paired-pulse facilitation; 30 mu M proline enhanced paired-pulse facilitation, whereas 3 mu M proline had no effect. In line with its enhancement of paired-pulse facilitation, 30 mu M proline reduced both the K+-evoked release of glutamate and aspartate from CA1 slices and the release of glutamate and aspartate from CA1 synaptosomes evoked by 4-aminopyridine. These results suggest that the proline-induced potentiation of Schaffer collateral-commissural synaptic transmission probably involves a postsynaptic, rather than a presynaptic, mechanism. Concentrations of proline normally found in human CSF little affect glutamate release. However, proline-induced inhibition of glutamate release may contribute to the neuropsychiatric disorders associated with hyperprolinemia type II. (C) 1997 Elsevier Science B.V.