Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, and Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
J Neurosci Res. 2010 Dec;88(16):3635-43. doi: 10.1002/jnr.22517. Epub 2010 Oct 8.
Even though induction of seizures by electroconvulsive stimulation (ECS) is a treatment widely used for major depression in humans, the working mechanism of ECS remains uncertain. The antiepileptic effect of ECS has been suggested to be involved in mediating the therapeutic effect of ECS. The neuropeptide galanin exerts antiepileptic and antidepressant-like effects and has also been implicated in the pathophysiology of depression. To explore a potential role of galanin in working mechanisms of ECS, the present study examined effects of repeated ECS on the galanin system using QRT-PCR, in situ hybridization, and [(125) I]galanin receptor binding. ECS was administered to adult mice daily for 14 days, and this paradigm was confirmed to exert antidepressant-like effect in the tail suspension test. Prominent increases in galanin gene expression were found in several brain regions involved in regulation of epileptic activity and depression, including the piriform cortex, hippocampal dentate gyrus, and amygdala. Likewise, GalR2 gene expression was up-regulated in both the central and the medial amygdala, whereas GalR1 gene expression showed a modest down-regulation in the medial amygdala. [(125) I]galanin receptor binding in the piriform cortex, hippocampus, and amygdala was found to be significantly down-regulated. These data show that the galanin system is regulated by repeated ECS in a number of brain regions implicated in seizure regulation and depression. These changes may play a role in the therapeutic effect of ECS.
尽管电惊厥刺激（ECS）诱发癫痫发作是一种广泛用于治疗人类重度抑郁症的方法，但 ECS 的工作机制仍不确定。ECS 的抗癫痫作用被认为参与介导 ECS 的治疗效果。神经肽甘丙肽具有抗癫痫和抗抑郁样作用，并且也与抑郁症的病理生理学有关。为了探索甘丙肽在 ECS 工作机制中的潜在作用，本研究使用 QRT-PCR、原位杂交和 [(125) I]甘丙肽受体结合研究了重复 ECS 对甘丙肽系统的影响。将 ECS 每日给予成年小鼠 14 天，该方案在悬尾试验中被证实具有抗抑郁样作用。在参与癫痫活动和抑郁调节的几个脑区中发现甘丙肽基因表达明显增加，包括梨状皮层、海马齿状回和杏仁核。同样，GalR2 基因表达在中央和内侧杏仁核中上调，而 GalR1 基因表达在内侧杏仁核中适度下调。在梨状皮层、海马和杏仁核中发现 [(125) I]甘丙肽受体结合显著下调。这些数据表明，甘丙肽系统在多个参与癫痫发作调节和抑郁的脑区中受到重复 ECS 的调节。这些变化可能在 ECS 的治疗效果中发挥作用。
