Fudge Julie L, Kelly Emily A, Mahoui Iman
Del Monte Institute for Neuroscience, Departments of Neuroscience and Psychiatry, University of Rochester Medical Center, Rochester, NY 14642, USA.
Genom Psychiatry. 2025 May;1(3):28-43. doi: 10.61373/gp025i.0038. Epub 2025 May 13.
Stress is a fact of life, affecting organisms from the smallest invertebrates to humans. Mediating the stress system is the ancient neuropeptide, corticotropin releasing factor (CRF), which works as a neuromodulator to alter brain systems and homeostatic responses to stress. In humans, many stress-related psychiatric illnesses are linked to dysregulation of monoamine systems, which have cross-talk with CRF-enriched circuits. In this review, we focus on the CRF and the midbrain dopamine (DA) system, particularly as it relates to the nonhuman primate. While tremendous knowledge of CRF-DA mechanisms has been gleaned from rodent models, treatments for stress-related diseases have been elusive, raising the question of whether higher animal models might be required. Subtle shifts in CRF peptide or CRF receptor localization, and the expansion and complexity of DA neuron populations, may hold some of the keys to understanding long-standing stress effects on the DA system in humans. Our laboratory has especially been interested in laying out the neural architecture of the CRF-DA system interface in the nonhuman primate, as a close anatomic model for human. Using rodent models as a starting point, we describe aspects of this complex system that inform our understanding of CRF-DA interactions, and focus on results that have been, and those that still need to be, translated to nonhuman primate models.
压力是生活中的一个现实，影响着从最小的无脊椎动物到人类的各种生物体。介导应激系统的是古老的神经肽促肾上腺皮质激素释放因子（CRF），它作为一种神经调节剂来改变大脑系统和对应激的稳态反应。在人类中，许多与压力相关的精神疾病与单胺系统的失调有关，而单胺系统与富含CRF的回路存在相互作用。在这篇综述中，我们聚焦于CRF和中脑多巴胺（DA）系统，特别是与非人灵长类动物相关的方面。虽然从啮齿动物模型中已经获得了关于CRF-DA机制的大量知识，但针对与压力相关疾病的治疗方法却难以捉摸，这就引发了是否需要更高等动物模型的问题。CRF肽或CRF受体定位的细微变化，以及DA神经元群体的扩展和复杂性，可能是理解长期压力对人类DA系统影响的一些关键所在。我们的实验室尤其关注构建作为人类紧密解剖模型的非人灵长类动物中CRF-DA系统界面的神经结构。以啮齿动物模型为起点，我们描述了这个复杂系统的一些方面，这些方面有助于我们理解CRF-DA相互作用，并聚焦于已经转化以及仍需转化为非人灵长类动物模型的研究结果。
