Cav1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype
Cav1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype
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DOI：
10.1017/s1461145709990368
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发表时间：
2010-05-01
影响因子：
4.8
通讯作者：
Singewald, Nicolas
中科院分区：
文献类型：
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作者：
Busquet, Perrine;Nguyen, Ngoc Khoi;Singewald, Nicolas
越来越多的证据表明，电压门控型L型钙通道可以调节情感行为。因此，我们利用Ca(V)1.3缺乏的小鼠(Ca-v-1.3(-/-))来探讨Ca(V)1.3 L类钙通道在抑郁和焦虑行为中的作用。我们发现，Ca(V)1.3(-/-)小鼠在强迫游泳试验和尾部悬吊试验中表现出较少的不动，这表明小鼠具有抗抑郁药样的表型。在家中笼子或新的开阔场地测试中的活动不受影响。在高架加迷宫(EPM)中，Ca(V)1.3(-/-)小鼠更频繁地进入张开的双臂，在那里停留的时间更长，这表明小鼠具有类似焦虑的表型，但在应激诱导的体温过高测试中并不支持这一表型。通过在Claudin 14基因敲除小鼠(CLDN14(-/-))上进行平行实验，可以排除耳聋对抗抑郁药样表型的影响。另一方面，在CLDN14(-/-)动物中也发现了类似的EPM行为，表明了一种缓解焦虑的表型。使用视网膜电图仪和视觉行为任务，我们证明了至少在小鼠中，钙-v-1.3通道对视觉功能没有显著贡献。然而，免疫组织化学显示，Ca(V)1.3(-/-)视网膜外丛状层的突触带有明显的形态变化，提示这种通道类型可能在突触带的结构可塑性中起作用。综上所述，我们的研究结果表明，Cav1.3 L类钙离子通道调节抑郁样行为，但对视觉功能不是必需的。这一发现提出了选择性调节Ca(V)1.3通道的可能性，这可能是治疗情绪障碍的一种有前途的新治疗概念。
Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of Ca(v)1.3 L-type Ca2+ channels in depression-and anxiety-like behaviours using Ca(v)1.3-deficient mice (Ca-v-1.3(-/-)). We showed that Ca(v)1.3(-/-) mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), Ca(v)1.3(-/-) mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14(-/-)), which like Ca(v)1.3(-/-) mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14(-/-) animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, Ca-v-1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of Ca(v)1.3(-/-) retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that Cav1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of Ca(v)1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.