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失神癫痫WAG/Rij大鼠中NMDA-NR1和AMPA-GluR4受体亚基的免疫反应性

NMDA-NR1 and AMPA-GluR4 receptor subunit immunoreactivities in the absence epileptic WAG/Rij rat.

作者信息

van de Bovenkamp-Janssen Maartje C, van der Kloet Joeri C, van Luijtelaar Gilles, Roubos Eric W

机构信息

Department of Cellular Animal Physiology, Institute for Neuroscience, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.

出版信息

Epilepsy Res. 2006 May;69(2):119-28. doi: 10.1016/j.eplepsyres.2006.01.003. Epub 2006 Feb 17.

DOI:10.1016/j.eplepsyres.2006.01.003
PMID:16487682
Abstract

From an age of 2-3 months onwards, the WAG/Rij rat, a genetic model for absence epilepsy, develops spike-wave discharges (SWD). SWD start in the peri-oral somatosensory cortex (POsc), whereas the rostral reticular thalamic nucleus (rRTN) contributes to synchronizing the thalamo-cortical oscillations. We hypothesize that N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors in the POsc and rRTN are involved in, respectively, the initiation and synchronization of SWD activity. As a first step to test this hypothesis, 3 months old non-epileptic and 6 months old absence epileptic WAG/Rij rats were compared with age-matched non-epileptic ACI control rats. The presence of NMDA and AMPA receptors was assessed by quantifying immunostaining for the NMDA-NR1 subunit and the AMPA-GluR4 subunit, respectively. In the POsc, WAG/Rij rats of both ages showed less NMDA-NR1 (-14.7%) and AMPA-GluR4 (-8.7%) subunit staining than ACI rats. From 3 to 6 months, AMPA-GluR4 subunit staining more strongly increased in the rRTN of WAG/Rij rats than of ACI rats. Further studies should support our assumption that in the POsc of the WAG/Rij rat, SWD start as a result of reduced NMDA- and AMPA-mediated glutamatergic stimulation, and that AMPA-GluR4 containing neurons in the rRTN of this rat strain contribute to synchronization of thalamic and cortical neurons.

摘要

从2 - 3个月大开始,失神癫痫的遗传模型WAG/Rij大鼠会出现棘波放电(SWD)。SWD始于口周体感皮层(POsc),而嘴侧网状丘脑核(rRTN)有助于丘脑 - 皮质振荡的同步化。我们假设POsc和rRTN中的N - 甲基 - D - 天冬氨酸(NMDA)和α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸(AMPA)受体分别参与SWD活动的起始和同步化。作为检验该假设的第一步,将3个月大的非癫痫性和6个月大的失神癫痫性WAG/Rij大鼠与年龄匹配的非癫痫性ACI对照大鼠进行比较。分别通过定量NMDA - NR1亚基和AMPA - GluR4亚基的免疫染色来评估NMDA和AMPA受体的存在情况。在POsc中,两个年龄段的WAG/Rij大鼠的NMDA - NR1亚基(-14.7%)和AMPA - GluR4亚基(-8.7%)染色均少于ACI大鼠。从3个月到6个月,WAG/Rij大鼠rRTN中AMPA - GluR4亚基染色的增加幅度比ACI大鼠更大。进一步的研究应支持我们的假设,即在WAG/Rij大鼠的POsc中,SWD的起始是由于NMDA和AMPA介导的谷氨酸能刺激减少,并且该大鼠品系rRTN中含有AMPA - GluR4的神经元有助于丘脑和皮质神经元的同步化。

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