Zavvari Fahime, Modarres Mousavi Sayed Mostafa, Ejlali Maryam, Barfi Shahram, Karimzadeh Fariba
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
Iran J Pharm Res. 2020 Fall;19(4):410-418. doi: 10.22037/ijpr.2020.112638.13869.
AMPA receptors, consisting of glutamate receptor type1 (GluR1) subunit are involved in the pathophysiology of some neurological disorders. In this study, the role of the GluR1 subunit in the development, as well as features of absence seizures were assessed. Both Wistar and WAG/Rij (a genetic animal model of absence epilepsy) rats with 2 and 6-month ages were included in the study. The expression of GluR1 was measured in the somatosensory cortex. Moreover, the effects of pharmacological activation and inhibition of AMPA receptors on the characteristic of absence epileptic activities were evaluated by microinjection of agonist or antagonist of AMPA receptors on the somatosensory cortex in the epileptic WAG/Rij rats. Distribution of the GluR1 subunit of AMPA receptors in the both IV ( 0.001) and VI ( 0.01) layers of the somatosensory cortex in the epileptic WAG/Rij rats was higher than non-epileptic animals. In addition, the microinjection of AMPA receptors agonist on the somatosensory cortex of the WAG/Rij rats increased both amplitude ( 0.01) and duration ( 0.001) of spike-wave discharges (SWDs), while injection of antagonist reduced amplitude ( 0.001) and duration ( 0.01) of SWDs in the somatosensory cortex of epileptic rats. The high expression of GluR1 in the somatosensory cortex of epileptic rats suggests the role of AMPA receptors consisting of the GluR1 subunit in the development of absence seizures. The modulatory effects AMPA receptors on the feature of SWDs suggest the potential of AMPA receptors antagonists as a therapeutic target for absence epilepsy.
由谷氨酸受体1型（GluR1）亚基组成的AMPA受体参与了某些神经系统疾病的病理生理过程。在本研究中，评估了GluR1亚基在发育过程中的作用以及失神发作的特征。研究纳入了2月龄和6月龄的Wistar大鼠以及WAG/Rij大鼠（失神癫痫的遗传动物模型）。检测了体感皮层中GluR1的表达。此外，通过向癫痫WAG/Rij大鼠的体感皮层微量注射AMPA受体激动剂或拮抗剂，评估了AMPA受体的药理激活和抑制对失神癫痫活动特征的影响。癫痫WAG/Rij大鼠体感皮层IV层（P<0.001）和VI层（P<0.01）中AMPA受体的GluR1亚基分布高于非癫痫动物。此外，向WAG/Rij大鼠的体感皮层微量注射AMPA受体激动剂可增加棘波放电（SWD）的幅度（P<0.01）和持续时间（P<0.001），而注射拮抗剂可降低癫痫大鼠体感皮层中SWD的幅度（P<0.001）和持续时间（P<0.01）。癫痫大鼠体感皮层中GluR1的高表达表明由GluR1亚基组成的AMPA受体在失神发作的发生中起作用。AMPA受体对SWD特征的调节作用表明AMPA受体拮抗剂作为失神癫痫治疗靶点的潜力。
