Shubina Liubov, Aliev Rubin, Kitchigina Valentina
Laboratory of Systemic Organization of Neurons, Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, 3 Institutskaya Str., Pushchino, Moscow Region 142290, Russian Federation.
Laboratory of Biophysics of Active Media, Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, 3 Institutskaya Str., Pushchino, Moscow Region 142290, Russian Federation; Computer Science Department, Moscow Institute of Physics and Technology, 9 Institutskiy Per., Dolgoprudny, Moscow Region 141700, Russian Federation.
Brain Res. 2017 Apr 15;1661:1-14. doi: 10.1016/j.brainres.2017.02.003. Epub 2017 Feb 10.
Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes. Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage. We employed wide frequency range (0.1-300Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction. To clarify whether the activation of endocannabinoid (eCB) system can influence toxic KA action, AM404, an eCB reuptake inhibitor, and URB597, an inhibitor of fatty acid amide hydrolase, were applied. The cannabinoid CB1 receptor antagonist AM251 was also tested. Coadministration of AM404 or URB597 with KA reduced acute behavioral seizures, but electrographic seizures were still registered. During the three months following KA injection, various trends in the oscillatory activities were observed, including an increase in activity power at all frequency bands in the hippocampus and a progressive long-term decrease in the medial septum. In the KA- and KA/AM251-treated animals, disturbances of the oscillatory activities were accompanied by cell loss in the dorsal hippocampus and mossy fiber sprouting in the dentate gyrus. Injections of AM404 or URB597 softened alterations in electrical activity of the brain and prevented hippocampal neuron loss and synaptic reorganization. Our results demonstrate the protective potential of the eCB system during excitotoxic influences.
节律性活动的变化可作为病理改变的早期生物标志物，但目前尚不清楚在神经退行性变过程中不同类型的节律性活动是如何改变的。由 kainic 酸（KA）诱发的谷氨酸能神经毒性会导致过度兴奋和急性癫痫发作，进而导致延迟性脑损伤。我们在豚鼠中采用宽频率范围（0.1 - 300Hz）的局部场电位记录，以研究 KA 引入后三个月内健康动物海马体、内嗅皮质、内侧隔和杏仁核的振荡活动。为了阐明内源性大麻素（eCB）系统的激活是否会影响有毒 KA 的作用，应用了 eCB 再摄取抑制剂 AM404 和脂肪酸酰胺水解酶抑制剂 URB597。还测试了大麻素 CB1 受体拮抗剂 AM251。AM404 或 URB597 与 KA 联合给药可减少急性行为性癫痫发作，但仍记录到脑电图癫痫发作。在 KA 注射后的三个月内，观察到振荡活动的各种趋势，包括海马体所有频段的活动功率增加以及内侧隔的长期逐渐下降。在 KA 和 KA/AM251 处理的动物中，振荡活动的紊乱伴随着背侧海马体中的细胞丢失和齿状回中的苔藓纤维发芽。注射 AM404 或 URB597 可减轻大脑电活动的改变，并防止海马神经元丢失和突触重组。我们的结果证明了 eCB 系统在兴奋性毒性影响期间的保护潜力。
