大麻素受体1信号通路在癫痫中作用的研究进展

Progress in research on the role of cannabinoid receptor 1 signaling pathway in epilepsy

癫痫是大脑神经元突发性异常放电所致短暂性大脑功能障碍的一种慢性神经系统疾病。自发的无端复发性癫痫发作以及学习、记忆障碍是其特征。癫痫发病机制非常复杂,目前尚未完全阐明。而中枢神经系统兴奋性谷氨酸能与抑制性γ-氨基丁酸(γ-aminobutyric acid, GABA)能神经递质间的平衡紊乱和N-甲基-D-天冬氨酸受体等离子通道功能的改变可直接诱导癫痫发作。内源性大麻素系统在逆行突触传递中起重要作用,并通过激活大麻素受体1(cannabinoid receptor 1, CBR1)信号通路在调节中枢神经系统谷氨酸能和GABA能神经递质传递,以及离子通道的稳态起到抗癫痫作用。因此,阐明CBR1信号通路在癫痫中的具体作用机制,可为临床治疗癫痫提供有效的理论依据和药物干预的靶点。

Epilepsy, a group of chronic neurological disorders characterized by spontaneous and recurrent seizures and learning and memory impairments, results in transient brain dysfunction due to sudden abnormal discharge of brain neurons. The pathogenesis of epilepsy is very complicated and has not yet been fully elucidated. The imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters in the central nervous system and changes in ionic functions of N-methyl-D-aspartate receptors directly induce epileptic seizures. The endocannabinoid system plays an important role in retrograde synaptic transmission and exerts the anti-epileptic effect in cannabinoid receptor 1 (CBR1) dependent manner by regulating the synaptic transmission of glutamatergic and GABAergic neurons and homeostatsis of ionic channel function. Elucidating the specific mechanism of action of CBR1 signaling pathway in epilepsy, can provide an effective theoretical basis and novel drug′s target for clinical treatment of epilepsy.