Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
Brain Res Bull. 2018 Mar;137:156-165. doi: 10.1016/j.brainresbull.2017.12.002. Epub 2017 Dec 11.
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.
焦虑障碍是一类以焦虑、紧张和恐惧等情绪为特征的精神障碍，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脑区。细胞质多聚腺苷酸化元件结合蛋白 1（CPEB1）介导 mRNA 多聚腺苷酸化尾的延伸，促进靶 RNA 的翻译。CPEB1 与神经元疾病密切相关，如脆性 X 综合征、学习记忆障碍和慢性疼痛。在这项研究中，确定了疼痛介导的焦虑小鼠模型中 CPEB1 在焦虑发展中的作用。通过向小鼠后足底注射完全弗氏佐剂（CFA）建立焦虑模型。CFA 注射导致焦虑样行为，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，这导致 BLA 中的 E/I 平衡紊乱，表现为增强的兴奋性突触前释放和减少的抑制性突触前释放。AAV-CPEB1-shRNA 降低 CPEB1 的表达减轻了模型小鼠的焦虑样行为，但对疼痛样行为没有影响，这是通过增强 BLA 中的抑制性传递实现的。数据表明，CPEB1 通过调节 BLA 中的兴奋/抑制性突触传递参与焦虑的发展。
