Bogovyk Ruslan, Lunko Oleksii, Fedoriuk Mihail, Isaev Dmytro, Krishtal Oleg, Holmes Gregory L, Isaeva Elena
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
Epilepsy Behav. 2017 Feb;67:66-69. doi: 10.1016/j.yebeh.2016.11.003. Epub 2017 Jan 13.
Protease-activated receptor 1 (PAR1) is an important contributor to the pathogenesis of a variety of brain disorders associated with a risk of epilepsy development. Using the lithium-pilocarpine model of temporal lobe epilepsy (TLE), we recently showed that inhibition of this receptor during the first ten days after pilocarpine-induced status epilepticus (SE) results in substantial anti-epileptogenic and neuroprotective effects. As PAR1 is expressed in the central nervous system regions of importance for processing emotional reactions, including amygdala and hippocampus, and TLE is frequently associated with a chronic alteration of the functions of these regions, we tested the hypothesis that PAR1 inhibition could modulate emotionally driven behavioral responses of rats experiencing SE. We showed that SE induces a chronic decrease in the animals' anxiety-related behavior and an increase of locomotor activity. PAR1 inhibition after SE abolished the alteration of the anxiety level but does not affect the increase of locomotor activity in the open field and elevated plus maze tests. Moreover, while PAR1 inhibition produces an impairment of memory recall in the context fear conditioning paradigm in the control group, it substantially improves contextual and cued fear learning in rats experiencing SE. These data suggest that PAR1-dependent signaling is involved in the mechanisms underlying emotional disorders in epilepsy.
蛋白酶激活受体1（PAR1）是多种与癫痫发生风险相关的脑部疾病发病机制的重要促成因素。利用颞叶癫痫（TLE）的锂-匹罗卡品模型，我们最近发现，在匹罗卡品诱导的癫痫持续状态（SE）后的前十天抑制该受体，会产生显著的抗癫痫发生和神经保护作用。由于PAR1在对处理情绪反应至关重要的中枢神经系统区域表达，包括杏仁核和海马体，且TLE常与这些区域功能的慢性改变相关，我们测试了PAR1抑制可调节经历SE的大鼠情绪驱动行为反应的假设。我们发现SE会导致动物焦虑相关行为的慢性减少和运动活动的增加。SE后抑制PAR1消除了焦虑水平的改变，但在旷场试验和高架十字迷宫试验中不影响运动活动的增加。此外，虽然PAR1抑制在对照组的情境恐惧条件范式中会损害记忆回忆，但它能显著改善经历SE的大鼠的情境和线索恐惧学习。这些数据表明，PAR1依赖性信号传导参与了癫痫中情绪障碍的潜在机制。
