GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala
GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala
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DOI：
10.1016/j.neuroscience.2011.08.069
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发表时间：
2011-11
期刊：
影响因子：
3.3
通讯作者：
L-l Zhang;Jing Wang;Yun Liu;Xb Lu;Y. Kuang;Ying-han Wan;Yuhong Chen;H-m Yan;J. Fei;Zhugang Wang
中科院分区：
文献类型：
--
作者：
L-l Zhang;Jing Wang;Yun Liu;Xb Lu;Y. Kuang;Ying-han Wan;Yuhong Chen;H-m Yan;J. Fei;Zhugang Wang
焦虑症是人类最常见和研究最多的精神疾病之一。已经建立了许多动物模型来研究焦虑的机制和测试假定的抗焦虑药物。Gpr 26属于G蛋白偶联受体家族，仅在脑组织中表达。为了研究Gpr 26在体内的生物学功能，我们已经产生了Gpr 26敲除小鼠。突变小鼠生长发育正常，但在旷场和高架十字迷宫试验中表现出焦虑样行为水平增加，在强迫游泳和悬尾试验中表现出更高水平的抑郁样行为。在Morris水迷宫实验中，Gpr 26基因缺陷小鼠的空间学习记忆能力无明显改变。先前的研究表明，杏仁核中较低的蛋白激酶A（PKA）-cAMP反应元件结合蛋白（CREB）-神经肽Y（NPY）信号转导与大鼠较高的焦虑和过度饮酒行为有关。因此，我们进一步检测了磷酸化CREB（pCREB）和Gpr 26缺陷小鼠脑中的CREB水平。在中央杏仁核中观察到pCREB水平降低，但在其他区域没有观察到，而野生型和突变小鼠之间的总CREB水平保持相当。结合，我们的数据表明，Gpr 26是重要的情绪调节小鼠，一个功能可能介导的中央杏仁核CREB的磷酸化。
Anxiety disorders are among the most common and well studied psychiatric disorders in humans. A number of animal models have been established to study the mechanisms of anxiety and to test putative anxiolytic drugs. Gpr26 belongs to the G-protein-coupled receptor family and is exclusively expressed in brain tissue. To investigate the biological function of Gpr26 in vivo, we have generated Gpr26 knockout mice. The mutant mice grew and developed normally but displayed increased levels of anxiety-like behaviors in the open field and elevated plus maze tests, as well as a higher level of depression-like behaviors in the forced-swim and tail-suspension tests. Meanwhile, no significant alteration in spatial learning and memory abilities were found for Gpr26-deficient mice in the Morris water maze test. Previous studies demonstrated that lower protein kinase A (PKA)–cAMP responsive element-binding protein (CREB)–neuropeptide Y (NPY) signaling in the amygdala is linked to higher anxiety and excessive alcohol-drinking behaviors in rats. Therefore, we further examined the phosphorylated CREB (pCREB) and CREB levels in the brains of Gpr26-deficient mice. Reduced pCREB levels were observed in the central amygdala but not in the other regions, while total CREB levels remained comparable between wild-type and mutant mice. Combined, our data indicate that Gpr26 is important for emotion regulation in mice, a function probably mediated by the phosphorylation of CREB in the central amygdala.