Anxiolytic effect of CPEB1 knockdown on the amygdala of a mouse model of inflammatory pain
Anxiolytic effect of CPEB1 knockdown on the amygdala of a mouse model of inflammatory pain
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CPEB1敲低对炎症性疼痛小鼠模型杏仁核的抗焦虑作用
DOI：
10.1016/j.brainresbull.2017.12.002
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发表时间：
2018-03-01
影响因子：
3.8
通讯作者：
Liu, Shui-bing
中科院分区：
文献类型：
--
作者：
Yue, Jiao;Wang, Xin-shang;Liu, Shui-bing
焦虑症是一类精神障碍，其特征是各种来源的焦虑、压力和恐惧感。但其发病机制复杂，尚未完全阐明。杏仁核是调节焦虑和精神障碍的重要大脑区域。细胞质多腺苷酸化元件结合蛋白 1 (CPEB1) 介导 mRNA 多腺苷酸化尾部的延伸并促进靶 RNA 的翻译。 CPEB1与脆性X综合征、学习记忆障碍、慢性疼痛等神经元疾病密切相关。在这项研究中，CPEB1 在焦虑发展中的作用是在疼痛介导的焦虑小鼠模型中确定的。通过后爪注射弗氏完全佐剂（CFA）建立小鼠焦虑模型。 CFA 注射随后导致类似焦虑的行为，并增加了小鼠基底外侧杏仁核 (BLA) 中的 CPEB1 水平。 CPEB1 增强促进了 GluA1、GluN2A、GluN2B、PSD95 和 GABA 受体的翻译，这扰乱了 BLA 中的 E/I 平衡，如兴奋性突触前释放增强和抑制性突触前释放减少所示。用 AAV-CPEB1-shRNA 敲低 CPEB1 通过增强模型小鼠 BLA 中的抑制传递来减轻焦虑样行为，但不能减轻疼痛样行为。数据表明，CPEB1 通过调节 BLA 中的兴奋性/抑制性突触传递来参与焦虑的发展。
Anxiety disorders are a category of mental disorders characterized by feelings of anxiety, stress, and fear attached to various sources. However, their pathogenesis is complicated and has not been fully elucidated. The amygdala is a vital brain region that regulates anxiety and mental disorders. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the extension of the mRNA polyadenylation tail and facilitates the translation of target RNA. CPEB1 is closely related to neuronal diseases, such as Fragile X Syndrome, learning and memory disorders, and chronic pain. In this study, the role of CPEB1 in anxiety development was determined in a pain-mediated anxiety mouse model. The anxiety model was established in mice by injecting with Complete Freund's Adjuvant (CFA) into the hindpaw. CFA injection then led to anxiety-like behaviors and increased the CPEB1 levels in the mouse basolateral amygdala (BLA). CPEB1 enhancement facilitated the translation of GluA1, GluN2A, GluN2B, PSD95, and GABA receptors, which disturbed the E/I balance in the BLA as shown by enhanced excitatory presynaptic release and reduced inhibitory presynaptic release. CPEB1 knockdown with AAV-CPEB1-shRNA alleviated the anxiety-like behaviors but not the pain-like behaviors by enhancing inhibitory transmission in the BLA of model mice. The data suggest that CPEB1 participates in anxiety development by regulating excitatory/inhibitory synaptic transmission in the BLA.