Common Pesticide Rotenone Interference with Neuronal Transmission in Hippocampus

Fatih Akkentli, Y. P. Tan, H. Saybaşılı
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引用次数: 2

Abstract

Rotenone is a pesticide and piscicide, wh ich causes behavioral and biochemical changes in rats that closely resemble PD sympto ms in hu mans. Rotenone is a naturally occurring ret inoid plant ext ract derived fro m the roots of certain tropical and subtropical legu me p lants and interferes with energy p roduction in the cell. Rotenone is highly lipophilic, so it can easily cross the blood brain barrier and cellular memb rane for intracellular entry.It is known that this pesticide causes superoxide release and results in decreased energy production by inhibiting electron transport chain of mitochondria fro m NADH ubiquinone reductaseand may lead to neuronal death. The object of the current research is to investigate the effect of rotenone on synaptic transmission in h ippocampus, especially on glutamatergic transmission for a b rief exposure time. For this purpose, hippocampal CA 1 pyramidal neuronal response upon low frequency stimulation of Schaffer collateral (0.1 Hz) was recorded by the patch clamp tight-seal whole cell recording technique. Different rotenone concentrations were tested on total glutamate current; it was observed that the rotenone effect on the amplitude of glutamatergic currents is dependent on its concentration. To eliminate the rotenone induced cytoplasmic effects, ATP was excluded fro m the intracellular solution in experiments. Our experimental results show that the drug acutely and dose-dependently attenuates the currents that are med iated by glutamate, v ia a direct effect on cell membrane g lutamate receptors.
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常见农药鱼藤酮对海马神经元传递的干扰
鱼藤酮是一种农药和杀虫剂,它引起大鼠的行为和生化变化,与人类PD症状非常相似。鱼藤酮是从某些热带和亚热带豆科植物的根中提取的一种天然存在的类植物提取物,可以干扰细胞中的能量产生。鱼藤酮是高度亲脂性的,因此它可以很容易地穿过血脑屏障和细胞膜进入细胞内。已知该农药通过抑制NADH泛醌还原酶的线粒体电子传递链导致超氧化物释放和能量产生减少,并可能导致神经元死亡。本研究的目的是研究鱼藤酮在长时间暴露下对海马突触传递,特别是对谷氨酸能传递的影响。为此,采用膜片钳紧封全细胞记录技术,记录海马ca1锥体神经元在低频刺激(0.1 Hz)时的反应。不同鱼藤酮浓度对总谷氨酸电流的影响;观察到鱼藤酮对谷氨酸电流振幅的影响取决于其浓度。为了消除鱼藤酮诱导的细胞质效应,实验中细胞内溶液中不含ATP。我们的实验结果表明,药物通过对细胞膜谷氨酸受体的直接作用,急性和剂量依赖性地减弱了谷氨酸介导的电流。
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