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首页> 外文期刊>Cerebral Cortex >Limbic Epileptogenesis in a Mouse Model of Fragile X Syndrome
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Limbic Epileptogenesis in a Mouse Model of Fragile X Syndrome

机译：易碎X综合征小鼠模型中的边缘癫痫发生。

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摘要

Fragile X syndrome (FXS), caused by silencing of the Fmr1 gene, is the most common form of inherited mental retardation. Epilepsy is reported to occur in 20–25% of individuals with FXS. However, no overall increased excitability has been reported in Fmr1 knockout (KO) mice, except for increased sensitivity to auditory stimulation. Here, we report that kindling increased the expressions of Fmr1 mRNA and protein in the forebrain of wild-type (WT) mice. Kindling development was dramatically accelerated in Fmr1 KO mice, and Fmr1 KO mice also displayed prolonged electrographic seizures during kindling and more severe mossy fiber sprouting after kindling. The accelerated rate of kindling was partially repressed by inhibiting N-methyl-D-aspartic acid receptor (NMDAR) with MK-801 or mGluR5 receptor with 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The rate of kindling development in WT was not effected by MPEP, however, suggesting that FMRP normally suppresses epileptogenic signaling downstream of metabolic glutamate receptors. Our findings reveal that FMRP plays a critical role in suppressing limbic epileptogenesis and predict that the enhanced susceptibility of patients with FXS to epilepsy is a direct consequence of the loss of an important homeostatic factor that mitigates vulnerability to excessive neuronal excitation.
机译：Fmr1基因沉默引起的脆性X综合征（FXS）是遗传性智力低下的最常见形式。据报道，癫痫发生在20-25％的FXS患者中。但是，除了增加对听觉刺激的敏感性外，在Fmr1基因敲除（KO）小鼠中没有报告总体兴奋性增加。在这里，我们报告说，点燃增加了野生型（WT）小鼠前脑中Fmr1 mRNA和蛋白的表达。在Fmr1 KO小鼠中，点燃过程得到显着加速，并且Fmr1 KO小鼠在点燃过程中也表现出长时间的电子癫痫发作，并且点燃后苔藓纤维发芽更加严重。通过用MK-801抑制N-甲基-D-天冬氨酸受体（NMDAR）或用2-甲基-6-（苯基乙炔基）-吡啶（MPEP）抑制mGluR5受体，部分抑制了点燃的加快速度。 MPEP不会影响WT的点燃发展速度，这表明FMRP通常会抑制代谢谷氨酸受体下游的致癫痫信号。我们的发现表明，FMRP在抑制边缘性癫痫发生中起关键作用，并预测FXS患者癫痫易感性的增强是失去重要的稳态因子的直接结果，该因子降低了过度神经元兴奋的脆弱性。

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  • 来源
    《Cerebral Cortex》 |2009年第7期|p.1504-1514|共11页
  • 作者

    Li-Feng Qiu1 Ting-Jia Lu1 Xiao-Ling Hu1 Yong-Hong Yi2 Wei-Ping Liao2 and Zhi-Qi Xiong1;

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    1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 2Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical College, Guangzhou 510260, China;

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