Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling
Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling
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DOI：
10.1007/s00018-018-2834-8
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发表时间：
2018-05
影响因子：
8
通讯作者：
Yuki Sugaya;M. Kano
中科院分区：
文献类型：
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作者：
Yuki Sugaya;M. Kano
内源性大麻素信号研究的进展极大地促进了我们对它如何控制健康和疾病中神经回路兴奋性的理解。一般来说，兴奋性突触的内源性大麻素信号通过抑制谷氨酸释放来抑制癫痫发作。相反，内源性大麻素信号通过抑制抑制性突触处的GABA释放来促进癫痫发作。内源性大麻素信号传导分子的生理分布随着内侧颞叶癫痫患者和实验诱导癫痫的动物模型中癫痫灶的发展而被破坏。内源性大麻素信号的增强可以在初始阶段促进癫痫灶的发展。然而，在后期阶段，增加内源性大麻素信号延迟它并抑制自发性癫痫发作。因此，在疾病发展的特定阶段引起过度兴奋的特定突触处的内源性大麻素信号传导的调节可能对治疗癫痫和癫痫发生有效。
Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.