Lasoń W, Turchan J, Przewłocka B, Labuz D, Machelska H, Przewłocki R
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.
Brain Res. 1998 Mar 2;785(2):355-8. doi: 10.1016/s0006-8993(97)01426-1.
It has been hypothesized that changes in the excitatory amino acid receptor biosynthesis may be involved in the mechanism of kindling-an animal model of epileptogenesis. In order to test this hypothesis, we investigated the effects of pentylenetetrazol kindling on the expression of genes coding for NMDAR1 and GluR2 in the rat hippocampal formation. Pentylenetetrazol kindling decreased the hippocampal NMDAR1 mRNA level after 3 and 24 h; lowered the GluR2 flip level and elevated the flop mRNA one in the CA1 field and dentate gyrus after 3 and 24 h, respectively. A receptor autoradiography showed an increase in the [3H]MK-801 binding density in the hippocampus following both acute and repeated pentylenetetrazol administration. We conclude that an early occurrence of downregulation of the glutamate receptor gene expression may be an adaptive response of glutamate receptors to an oversupply of excitatory amino acids during repeated seizures.
据推测，兴奋性氨基酸受体生物合成的变化可能参与点燃效应（一种癫痫发生的动物模型）的机制。为了验证这一假设，我们研究了戊四氮点燃对大鼠海马结构中编码NMDAR1和GluR2的基因表达的影响。戊四氮点燃在3小时和24小时后降低了海马NMDAR1 mRNA水平；分别在3小时和24小时后降低了CA1区和齿状回中GluR2翻转异构体水平，并提高了其摆动异构体mRNA水平。受体放射自显影显示，急性和重复给予戊四氮后，海马中[3H]MK-801结合密度增加。我们得出结论，谷氨酸受体基因表达下调的早期出现可能是谷氨酸受体对反复癫痫发作期间兴奋性氨基酸供应过多的一种适应性反应。
