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血管活性肠肽(VIP)在失神发作期间控制神经元活动:GABA 似乎是 VIP 的主要介导物。

Vasoactive intestinal peptide (VIP) conducts the neuronal activity during absence seizures: GABA seems to be the main mediator of VIP.

机构信息

Department of Physiology, Faculty of Medicine, Eskisehir Osmangazi University, 26040 Eskisehir, Turkey.

Department of Physiology, Medical Faculty, Kocaeli University, 41380, Kocaeli, Turkey.

出版信息

Neurosci Lett. 2021 Nov 20;765:136268. doi: 10.1016/j.neulet.2021.136268. Epub 2021 Sep 24.

Abstract

Absence epilepsy is classified as a childhood generalized epilepsy syndrome with distinctive electroencephalographic patterns. The Wistar Albino Glaxo originating from Rijswijk (WAG/Rij) strain is a very well validated animal model of absence epilepsy that also shows behavioral deficits. In addition to the gastrointestinal system, VIP is highly expressed throughout numerous brain regions, and it plays crucial roles as a neurotransmitter and as a neuromodulatory, neurotrophic and neuroprotective factor in both the central and peripheral nervous systems. In this study, adult WAG/Rij rats were divided into two groups (n = 10): a group that was administered VIP (25 ng/kg i.p.) every 2 days for 15 days and an age-matched control group that was administered physiological saline. Electrical brain activity and behavior (depressive- like behavior, learning and memory and anxiety) were investigated in both groups. In addition, the extracellular concentrations of GABA and glutamate and the GABA/glutamate ratio were measured by high-performance liquid chromatography in microdialysate samples collected from the somatosensorial cortex of WAG/Rij rats. Our results demonstrated that VIP treatment significantly suppressed the total duration and number of spike wave discharges in WAG/Rij rats. However, VIP had no significant effect on behavior. VIP increased the extracellular concentration of GABA and the GABA/glutamate ratio in the somatosensory cortex. In conclusion, VIP has suppressive effects on absence seizures, possibly by increasing the GABA concentration and inducing the transformation of glutamate to GABA in the somatosensory cortex of WAG/Rij rats.

摘要

失神发作被归类为具有独特脑电图模式的儿童全面性癫痫综合征。 源自 Rijswijk(WAG/Rij)的 Wistar Albino Glaxo 品系是一种经过充分验证的失神癫痫动物模型,也表现出行为缺陷。除了胃肠道系统外,VIP 在许多脑区都有高表达,它作为神经递质以及在中枢和外周神经系统中作为神经调质、神经营养和神经保护因子发挥着关键作用。在这项研究中,成年 WAG/Rij 大鼠被分为两组(n = 10):一组每隔两天给予 VIP(25ng/kg 腹腔注射),共 15 天;另一组为年龄匹配的对照组,给予生理盐水。对两组大鼠进行电脑活动和行为(抑郁样行为、学习和记忆以及焦虑)的研究。此外,通过高效液相色谱法测量微透析样本中 GABA 和谷氨酸的细胞外浓度以及 GABA/谷氨酸比值。我们的结果表明,VIP 治疗显著抑制了 WAG/Rij 大鼠的总发作持续时间和棘波放电次数。然而,VIP 对行为没有显著影响。VIP 增加了体感皮层中 GABA 的细胞外浓度和 GABA/谷氨酸比值。总之,VIP 对失神发作具有抑制作用,可能是通过增加 GABA 浓度并诱导谷氨酸向 GABA 的转化在 WAG/Rij 大鼠的体感皮层中实现的。

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