红藻氨酸诱导大鼠癫痫发作时海马mGluR5 mRNA表达变化的动态观察

Dynamic changes of mGluR5 mRNA expression in rat hippocampus during seizures induced by kainic acid

目的 探讨红藻氨酸 (KA,10 mg·kg- 1 )诱导大鼠癫痫发作时海马代谢型谷氨酸受体 5亚型 (m Glu R5 ) m RNA表达变化的病理特征 .方法 采用同位素 S35 d ATP标记寡核苷酸探针原位杂交法检测大鼠癫痫发作前后海马 m Glu R5m RNA的表达变化 ,通过图像分析系统进行定量处理 .同时观察大鼠行为学及脑电变化 .结果 KA注射后大鼠均出现严重边缘性惊厥 ,脑电图表现为阵发性癫痫样放电 .正常大鼠海马中有丰富的 m Glu R5 m RNA表达 ,以齿状回和 CA1区表达较高 .KA注射后海马各区 m Glu R5 m RNA表达呈时间依赖性下调 ,CA1,CA3,CA4区表达在 2 h呈现出显著性差异 (P<0 .0 5 ) ,齿状回区表达在 1h即有显著性差异 (P<0 .0 1) ,至 72 h各区表达均至最低 .结论 m Glu R5在癫痫发作后表达下降可能有助于限制神经元网络的异常兴奋性 。

AIM To investigate temporospatial changes of metabotropic glutamate receptor subtype 5 (mGluR5) mRNA expression in rat hippocampus during seizures induced by kainic acid (KA). METHODS Using in situ hybridization with S 35 dATP labelled oligodeoxyribonucleotide probes, mGluR5 mRNA expression was examined. The relative number of hybridization signals was quantified by image analysis systems. The electroencephalogram (EEG) and behaviour changes of the rats were simultaneously observed. RESULTS All rats of KA injected group exhibited severe limbic convulsions. The EEG recordings also showed electrical seizure activities. mGluR5 mRNA was widely expressed in rat hippocampus with the higher levels in the granular layer of the dentate gyrus and the pyramidal layer of CA1. After KA injection, mGluR5 mRNA expression exhibited time dependent downregulation. Area scanning revealed that mGluR5 mRNA was markedly downregulated at 2 h in CA1, CA3 and CA4 ( P <0.05), but in dentate gyrus at 1 h ( P <0.01). At 72 h, it reached the lowest level. CONCLUSION KA induced seizures modifies mGluR5 gene expression, which may help to limit abnormal excitability of neuronal network.