Altered glutamate receptor-transporter expression and spontaneous seizures in rats exposed to methylazoxymethanol in utero
Altered glutamate receptor-transporter expression and spontaneous seizures in rats exposed to methylazoxymethanol in utero
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DOI：
10.1111/j.1528-1167.2006.00838.x
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发表时间：
2007-01-01
期刊：
影响因子：
5.6
通讯作者：
Baraban, Scott C.
中科院分区：
文献类型：
--
作者：
Harrington, Emily P.;Moddel, Gabriel;Baraban, Scott C.
目的：脑畸形是儿童顽固性癫痫和认知功能障碍的常见原因。产前暴露于致畸原甲基氧化甲醇（MAM）是一种啮齿动物脑畸形模型，其特征是层压丧失，海马细胞簇移位，以及对抗癫痫药物的耐药性。在正常海马中，突触后谷氨酸受体的表达和调节神经递质再摄取的转运体是调节兴奋和突触通讯的关键因素。该系统的改变可对整体兴奋性、认知功能和癫痫阈值产生深远影响。方法：采用免疫组织化学技术分析MAM （25 mg/kg，腹腔注射）大鼠子宫暴露后n -甲基- d -天冬氨酸（NMDA）和α -氨基-3-羟基-5甲基异唑-4-丙酸（AMPA）受体亚基的表达。我们还检测了几种谷氨酸转运蛋白（EAAC1、vGLUT1和vGLUT2）的表达。采用视频脑电图（video-EEG）系统对成年暴露于mam的大鼠进行长期监测。结果：异位海马神经元GluR1和EAAC1表达显著降低；vGlut2在这些区域表达显著。自发性电痉挛在两只动物中得到证实。结论：我们得出谷氨酸受体亚基和转运体表达在子宫内暴露于MAM的动物中发生改变。对MAM模型的进一步研究可能会对畸形大脑中可能发生的兴奋性突触神经传递的潜在中断提供更深入的了解。
Purpose: Brain malformations are a common cause of intractable epilepsy and cognitive dysfunction in children. Prenatal exposure to the teratogen methylazoxymethanol (MAM) is a rodent model of brain malformation featuring loss of lamination, clusters of displaced hippocampal cells, and pharmaco-resistance to antiepileptic drugs. In a normotopic hippocampus, expression of postsynaptic glutamate receptors and the transporters regulating neurotransmitter reuptake are critical factors modulating excitation and synaptic communication. Alterations in this system can have profound effects on overall excitability, cognitive function, and seizure thresholds.Methods: Immunohistochemical techniques were used to analyze the expression of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5 methylisoxazole-4-proprionic acid (AMPA) receptor subunits in rats exposed to MAM in utero (25 mg/kg, intraperitoneal injection). We also examined the expression of several glutamate transporters (EAAC1, vGLUT1, and vGLUT2). A video-electroencephalographic (video-EEG) system was used for long-term monitoring of adult MAM-exposed rats.Results: Heterotopic hippocampal neurons exhibited striking reductions in GluR1 and EAAC1 expression; vGlut2 expression was prominent in these regions. Spontaneous electrographic seizures were verified in two animals.Conclusions: We conclude that glutamate receptor subunit and transporter expression are altered in animals exposed to MAM in utero. Further studies in the MAM model may provide greater insight into the potential disruptions in excitatory synaptic neurotransmission that can occur in a malformed brain.