Yang Xin, Geng Fei
Department of Physiology, Shantou University Medical College, Shantou, China.
Department of Transfusion Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
J Neurosci Res. 2023 Dec;101(12):1781-1794. doi: 10.1002/jnr.25238. Epub 2023 Aug 18.
A large body of literature has highlighted the significance of the corticotropin-releasing factor (CRF) system in the regulation of neuropsychiatric diseases. Anxiety disorders are among the most common neuropsychiatric disorders. An increasing number of studies have demonstrated that the CRF family mediates and regulates the development and maintenance of anxiety. Thus, the CRF family is considered to be a potential target for the treatment of anxiety disorders. The prefrontal cortex (PFC) plays a role in the occurrence and development of anxiety, and both CRF and CRF-R1 are widely expressed in the PFC. This paper begins by reviewing CRF-related signaling pathways and their different roles in anxiety and related processes. Then, the role of the CRF system in other neuropsychiatric diseases is reviewed and the potential role of PFC CRF signaling in the regulation of anxiety disorders is discussed. Although other signaling pathways are potentially involved in the process of anxiety, CRF in the PFC primarily modulates anxiety disorders through the activation of corticotropin-releasing factor type1 receptors (CRF-R1) and the excitation of the cAMP/PKA signaling pathway. Moreover, the main signaling pathways of CRF involved in sex differentiation in the PFC appear to be different. In summary, this review suggests that the CRF system in the PFC plays a critical role in the occurrence of anxiety. Thus, CRF signaling is of great significance as a potential target for the treatment of stress-related disorders in the future.
大量文献强调了促肾上腺皮质激素释放因子（CRF）系统在神经精神疾病调节中的重要性。焦虑症是最常见的神经精神疾病之一。越来越多的研究表明，CRF家族介导并调节焦虑的发生和维持。因此，CRF家族被认为是治疗焦虑症的潜在靶点。前额叶皮质（PFC）在焦虑的发生和发展中起作用，CRF和CRF-R1在PFC中均广泛表达。本文首先综述与CRF相关的信号通路及其在焦虑和相关过程中的不同作用。然后，综述CRF系统在其他神经精神疾病中的作用，并讨论PFC中CRF信号在焦虑症调节中的潜在作用。尽管其他信号通路可能参与焦虑过程，但PFC中的CRF主要通过激活1型促肾上腺皮质激素释放因子受体（CRF-R1）和激活cAMP/PKA信号通路来调节焦虑症。此外，PFC中涉及性别分化的CRF主要信号通路似乎有所不同。总之，本综述表明PFC中的CRF系统在焦虑发生中起关键作用。因此，CRF信号作为未来治疗应激相关疾病的潜在靶点具有重要意义。
