Targeting the endocannabinoid system in the amygdala kindling model of temporal lobe epilepsy in mice
Targeting the endocannabinoid system in the amygdala kindling model of temporal lobe epilepsy in mice
复制标题
靶向小鼠颞叶癫痫杏仁核点燃模型中的内源性大麻素系统
DOI：
10.1111/j.1528-1167.2011.03079.x
复制
发表时间：
2011
期刊：
影响因子：
5.6
通讯作者：
H Potschka
中科院分区：
文献类型：
--
作者：
Wendt H;Soerensen J;Wotjak CT;H Potschka
内源性大麻素系统可以被认为是一个假定的目标，影响发作以及产生一个过度兴奋的癫痫网络。因此，我们评估了CB 1受体激动剂（WIN55.212 - 2）和内源性大麻素anandamide酶降解抑制剂（脂肪酸水解酶抑制剂URB 597）在颞叶癫痫杏仁核点燃模型中的作用。在完全点燃小鼠中仅观察到对癫痫发作阈值和癫痫发作参数的轻微影响，无明显剂量依赖性。在评价对点燃获得的影响时，WIN55.212‐2显著延迟了癫痫发作严重程度的进展。相反，URB 597不影响点燃范式中癫痫发作的发展。点燃过程中细胞增殖和神经发生的分析表明，URB 597显着减少了新生神经元的数量。这些数据提供了第一个证据，表明CB 1受体激活可能会产生一种疾病修饰方法。未来的研究需要进一步分析CB 1受体的作用，并确认CB 1受体激动剂在其他慢性癫痫模型中的疗效。
The endocannabinoid system can be considered as a putative target to affect ictogenesis as well as the generation of a hyperexcitable epileptic network. Therefore, we evaluated the effect of a CB1 receptor agonist (WIN55.212‐2) and of an inhibitor of the enzymatic degradation of the endocannabinoid anandamide (fatty acid hydrolase inhibitor URB597) in the amygdala kindling model of temporal lobe epilepsy. Only minor effects on seizure thresholds and seizure parameters without a clear dose‐dependency were observed in fully kindled mice. When evaluating the impact on kindling acquisition, WIN55.212‐2 significantly delayed the progression of seizure severity. In contrast, URB597 did not affect the development of seizures in the kindling paradigm. Analysis of cell proliferation and neurogenesis during the kindling process revealed that URB597 significantly reduced the number of newborn neurons. These data give first evidence that CB1‐receptor activation might render a disease‐modifying approach. Future studies are necessary that further analyze the role of CB1 receptors and to confirm the efficacy of CB1‐receptor agonists in other models of chronic epilepsy.
DOI：
10.1124/jpet.103.051920
发表时间：
2003-10-01
影响因子：
3.5
作者：
Wallace, MJ;Blair, RE;DeLorenzo, RJ
通讯作者：
DeLorenzo, RJ
内源性大麻素在调节癫痫阈值和严重程度中的生理作用的证据。
影响因子：
5
作者：
Wallace,MelisaJ;Martin,BillyR;DeLorenzo,RobertJ
通讯作者：
DeLorenzo,RobertJ