Changes in AMPA receptor binding and subunit messenger RNA expression in hippocampus and cortex in the pentylenetetrazole-induced 'kindling' model of epilepsy
Changes in AMPA receptor binding and subunit messenger RNA expression in hippocampus and cortex in the pentylenetetrazole-induced 'kindling' model of epilepsy
复制标题
DOI：
10.1016/s0169-328x(01)00230-3
复制
发表时间：
2001-11-01
期刊：
影响因子：
--
通讯作者：
Angelatou, F
中科院分区：
文献类型：
--
作者：
Ekonomou, A;Smith, AL;Angelatou, F
“点燃”是一种癫痫发生现象，被广泛用作颞叶癫痫的实验模型。在本研究中，我们通过定量放射自显影和原位杂交，研究了α -氨基-3-羟基-5-甲基异唑-4-丙酸（AMPA）谷氨酸受体及其亚基（GluR-A, -B， -C和-D）在戊四唑（PTZ）诱导的“点燃”小鼠模型中获得和维持点燃状态的贡献。最后一次PTZ注射1周后，点燃动物海马CA3区和颞叶皮层[H-3]AMPA结合区域特异性增加。同时，在海马CA1区和齿状回中检测到编码GluR-B和c亚基的转录本水平显著下降，这表明这些神经元中Ca2+渗透性AMPA受体的比例更高。这些变化在点燃后1个月没有持续，表明AMPA受体在获得点燃状态中的作用是短暂的。在最后一次PTZ注射后1个月，点燃动物的运动皮层和基底节区出现[H-3]AMPA结合上调，这与当时PTZ点燃动物皮层高兴奋性的电生理数据一致。有趣的是，在获得点燃状态1个月后，点燃动物的运动和体感皮层的外层出现了GluR-B亚基mRNA的增加，可能是基因调控的一部分，对抗癫痫易感性的代偿机制，因为这种变化应该引起更高比例的Ca2+不渗透AMPA受体。这些结果支持了海马AMPA受体在获得“点燃”现象中的短暂作用的证据，它们还表明AMPA受体至少在大脑皮层和基底神经节两个区域参与了点燃状态的维持。(C) 2001年Elsevier Science by出版。
"Kindling' is a phenomenon of epileptogenesis, which has been widely used as an experimental model of temporal lobe epilepsy. In the present study, we have examined the contribution of alpha -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors and their subunits (GluR-A, -B, -C and -D) to the acquisition and maintenance of the kindled state in the pentylenetetrazole (PTZ)-induced 'kindling' mouse model, by using quantitative autoradiography and in situ hybridization. Region-specific increases in [H-3]AMPA binding were seen in kindled animals in the CA3 region of hippocampus and in the temporal cortex 1 week after the last PTZ injection. At the same time, a significant decrease in the level of transcripts encoding the GluR-B and -C subunits was detected in the hippocampal CA1 region and dentate gyrus, suggestive of a higher proportion of Ca2+-permeable AMPA receptors in these neurons.' These changes did not persist 1 month after establishment of kindling, indicating a transient role of AMPA receptors in the acquisition of the kindled state. At 1 month after the last PTZ injection, an upregulation in [H-3]AMPA binding appeared in the motor cortex and the basal ganglia of kindled animals, which is consistent with electrophysiological data showing hyperexcitability in the cortex of the PTZ-kindled animals at that time. Interestingly, an increase in mRNA for the GluR-B subunit appeared in the outer layers of motor and somatosensory cortices of the kindled animals 1 month after acquisition of the kindled state, possibly as part of a gene-regulated, compensatory mechanism against seizure susceptibility, since this change should give rise to a higher proportion of Ca2+-impermeable AMPA receptors. These results support the evidence of a transient role of hippocampal AMPA receptors in the acquisition of the `kindling' phenomenon and they also suggest an involvement of AMPA receptors in the maintenance of kindled state at least in two brain areas, cortex and basal ganglia. (C) 2001 Published by Elsevier Science BY.