Medina-Ceja Laura, García-Barba Carla
Laboratory of Neurophysiology, Department of Cellular and Molecular Biology, CUCBA, University of Guadalajara, Jalisco, Mexico.
Laboratory of Neurophysiology, Department of Cellular and Molecular Biology, CUCBA, University of Guadalajara, Jalisco, Mexico.
Neurosci Lett. 2017 Aug 10;655:137-142. doi: 10.1016/j.neulet.2017.06.056. Epub 2017 Jun 30.
Fast ripples (FR) are high frequency oscillations (250-600Hz) that have been associated with epilepsy. FR are assumed to be generated in small areas of the hippocampus (1mm) that contain pathologically interconnected glutamate pyramidal cell clusters. Additionally, a relation between glutamate neurotransmission and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainite (AMPA/KA) and metabotropic mGluR5 receptors is well established. Therefore, we hypothesized that antagonism of these glutamate receptors would decrease FR activity. For this propose, we induced status epilepticus with a kainic acid injection in the posterior right hippocampus and performed intracranial EEG recordings to detect and evaluate the presence of FR 15days after the injection. The glutamate AMPA/KA receptor antagonist CNQX (10mg/kg) and the mGluR5 antagonist MPEP (20mg/kg) were administered intraperitoneally, and the effects of the drugs were evaluated for a period of three hours after their administration. The results show a decrease in the number of FR in the first hour after drug administration in both cases (CNQX, p=0.0125; MPEP, p=0.0132) and a return to basal values in the third hour of the experiment, but not significant differences in the number of oscillations per event of FR, and the frequency and duration of each event of FR. We therefore conclude that blockade of AMPA/KA and mGluR5 receptors transiently decreases the generation of FR; however, the mechanisms by which this effect is achieved are to be further analyzed in future experiments.
快速涟漪（FR）是与癫痫相关的高频振荡（250 - 600Hz）。FR被认为是在海马体的小区域（1毫米）产生的，这些区域包含病理上相互连接的谷氨酸能锥体细胞簇。此外，谷氨酸能神经传递与α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸/海人藻酸（AMPA/KA）以及代谢型谷氨酸受体5（mGluR5）之间的关系已得到充分证实。因此，我们假设拮抗这些谷氨酸受体将降低FR活性。为此，我们通过在右侧后海马体注射海人藻酸诱导癫痫持续状态，并在注射后15天进行颅内脑电图记录以检测和评估FR的存在。腹腔注射谷氨酸AMPA/KA受体拮抗剂CNQX（10mg/kg）和mGluR5拮抗剂MPEP（20mg/kg），并在给药后三小时评估药物的效果。结果显示，在给药后的第一个小时，两种情况下FR的数量均减少（CNQX，p = 0.0125；MPEP，p = 0.0132），并且在实验的第三个小时恢复到基础值，但FR每次事件的振荡次数、每个FR事件的频率和持续时间没有显著差异。因此，我们得出结论，阻断AMPA/KA和mGluR5受体会短暂降低FR的产生；然而，实现这种效果的机制将在未来的实验中进一步分析。
