Chiprés-Tinajero Gustavo A, Núñez-Ochoa Miguel A, Medina-Ceja Laura
Laboratory of Neurophysiology, Department of Cellular and Molecular Biology, CUCBA, University of Guadalajara, Camino Ing. R. Padilla Sánchez 2100, Las Agujas, Nextipac, Zapopan, Jalisco, 45110, México.
Exp Brain Res. 2021 Jun;239(6):2015-2024. doi: 10.1007/s00221-021-06108-6. Epub 2021 Apr 28.
Epilepsy is a neurological disorder in which an imbalance between excitatory and inhibitory transmission is observed. Glutamate is the principal excitatory neurotransmitter that acts through ionic and metabotropic receptors; both types of receptors are involved in temporal lobe epilepsy (TLE). High frequency oscillations called fast ripples (FR, 250-600 Hz) have been observed, particularly in the hippocampus, and they are involved in epileptogenesis. The present study analyzed the immunoreactivity of the principal glutamate receptors associated with epilepsy in epileptic animals with FR activity. Male Swiss-Wistar rats (210-250 gr) were injected with pilocarpine (2.4 mg/2 µl) and were video monitored (24/7) until the appearance of spontaneous and recurrent seizures. Then, a deep microelectrode implantation surgery was performed in the DG, CA3 and CA1 regions, and FR activity was observed 1-, 2-, 3-, 7-, and 14-day postsurgery. The animals were sacrificed on day 15, and fluorescence immunohistochemistry was carried out in the hippocampus for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and mGlu-R5 glutamate receptors as well as Neuronal Nuclear Protein (NeuN) and Glial Fibrillary Acidic Protein (GFAP). An increase in the immunoreactivity for the three receptors was found. However, the AMPA receptor showed an increase in the three regions analyzed (i.e., DG, CA1 and CA3). The findings showed a decrease of NeuN in the DG and an increase of GFAP. These results suggest an important role of glutamate receptors in the hippocampus of epileptic rats with FR activity.
癫痫是一种神经系统疾病,其特征是兴奋性和抑制性神经传递之间失衡。谷氨酸是主要的兴奋性神经递质,通过离子型和代谢型受体发挥作用;这两种受体均与颞叶癫痫(TLE)有关。已观察到高频振荡,即快速涟漪(FR,250 - 600 Hz),尤其是在海马体中,并且它们参与癫痫发生过程。本研究分析了具有FR活动的癫痫动物中与癫痫相关的主要谷氨酸受体的免疫反应性。将雄性瑞士-维斯特大鼠(210 - 250克)注射匹鲁卡品(2.4毫克/2微升),并进行24/7视频监测,直至出现自发和反复癫痫发作。然后,在齿状回(DG)、CA3和CA1区域进行深部微电极植入手术,并在术后1天、2天、3天、7天和14天观察FR活动。在第15天处死动物,并在海马体中对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)、N-甲基-D-天冬氨酸(NMDA)和代谢型谷氨酸受体5(mGlu-R5)以及神经元核蛋白(NeuN)和胶质纤维酸性蛋白(GFAP)进行荧光免疫组织化学检测。发现三种受体的免疫反应性均增加。然而,AMPA受体在分析的三个区域(即DG、CA1和CA3)均显示增加。结果显示DG中NeuN减少,GFAP增加。这些结果表明谷氨酸受体在具有FR活动的癫痫大鼠海马体中起重要作用。