Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Neurobiol Dis. 2012 Jan;45(1):288-96. doi: 10.1016/j.nbd.2011.08.012. Epub 2011 Aug 22.
We recently demonstrated that recombinant adeno-associated viral vector-induced hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure-suppressant effect in kindling and kainate-induced models of epilepsy in rats. Interestingly, additional overexpression of neuropeptide Y in the hippocampus strengthened the seizure-suppressant effect of transgene Y2 receptors. Here we show for the first time that another neuropeptide Y receptor, Y5, can also be overexpressed in the hippocampus. However, unlike Y2 receptor overexpression, transgene Y5 receptors in the hippocampus had no effect on kainate-induced motor seizures in rats. However, combined overexpression of Y5 receptors and neuropeptide Y exerted prominent suppression of seizures. This seizure-suppressant effect of combination gene therapy with Y5 receptors and neuropeptide Y was significantly stronger as compared to neuropeptide Y overexpression alone. These results suggest that overexpression of Y5 receptors in combination with neuropeptide Y could be an alternative approach for more effective suppression of hippocampal seizures.
我们最近的研究表明，重组腺相关病毒载体诱导海马区神经肽 Y 受体 Y2 的过表达，对大鼠的点燃和海人酸诱导的癫痫模型具有抑制癫痫发作的作用。有趣的是，海马区神经肽 Y 的额外过表达增强了转基因 Y2 受体的抑制癫痫发作作用。在这里，我们首次表明，另一种神经肽 Y 受体 Y5 也可以在海马区过表达。然而，与 Y2 受体过表达不同，海马区的转基因 Y5 受体对大鼠海人酸诱导的运动性癫痫发作没有影响。然而，Y5 受体和神经肽 Y 的联合过表达显著抑制了癫痫发作。与单独过表达神经肽 Y 相比，Y5 受体和神经肽 Y 的联合基因治疗的这种抑制癫痫发作作用明显更强。这些结果表明，Y5 受体与神经肽 Y 的过表达相结合可能是一种更有效的抑制海马区癫痫发作的替代方法。
