Smith Whitnei, Azevedo Estefania P
Laboratory of Neurobiology of Behavior, Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
J Neurochem. 2025 Feb;169(2):e70006. doi: 10.1111/jnc.70006.
Stress, an evolutionarily adaptive mechanism, has become a pervasive challenge in modern life, significantly impacting feeding-relevant circuits that play a role in the development and pathogenesis of eating disorders (EDs). Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, disrupts specific neural circuits, and dysregulates key brain regions, including the hypothalamus, hippocampus, and lateral septum. These particular structures are interconnected and key in integrating stress and feeding signals, modulating hunger, satiety, cognition, and emotional coping behaviors. Here we discuss the interplay between genetic predispositions and environmental factors that may exacerbate ED vulnerability. We also highlight the most commonly used animal models to study the mechanisms driving EDs and recent rodent studies that emphasize the discovery of novel cellular and molecular mechanisms integrating stress and feeding signals within the hippocampus-lateral septum-hypothalamus axis. In this review, we discuss the role of gut microbiome, an emerging area of research in the field of EDs and unanswered questions that persist and hinder the scientific progress, such as why some individuals remain resilient to stress while others become at high risk for the development of EDs. We finally discuss the need for future research delineating the impact of specific stressors on neural circuits, clarifying the relevance and functionality of hippocampal-septal-hypothalamic connectivity, and investigating the role of key neuropeptides such as CRH, oxytocin, and GLP-1 in human ED pathogenesis. Emerging tools like single-cell sequencing and advanced human imaging could uncover cellular and circuit-level changes in brain areas relevant for feeding in ED patients. Ultimately, by integrating basic and clinical research, science offers promising avenues for developing personalized, mechanism-based treatments targeting maladaptive eating behavior for patients suffering from EDs.
压力作为一种进化上的适应性机制，已成为现代生活中普遍存在的挑战，对与进食相关的神经回路产生重大影响，这些回路在饮食失调（EDs）的发展和发病机制中发挥作用。压力会激活下丘脑 - 垂体 - 肾上腺（HPA）轴，破坏特定的神经回路，并使包括下丘脑、海马体和外侧隔区在内的关键脑区调节失调。这些特定结构相互连接，对于整合压力和进食信号、调节饥饿感、饱腹感、认知和情绪应对行为至关重要。在这里，我们讨论了可能加剧饮食失调易感性的遗传倾向与环境因素之间的相互作用。我们还重点介绍了用于研究饮食失调驱动机制的最常用动物模型，以及最近的啮齿动物研究，这些研究强调了在海马体 - 外侧隔区 - 下丘脑轴内整合压力和进食信号的新型细胞和分子机制的发现。在这篇综述中，我们讨论了肠道微生物群的作用，这是饮食失调领域一个新兴的研究领域，以及持续存在并阻碍科学进展的未解决问题，比如为什么有些人对压力具有抵抗力，而另一些人却有很高的饮食失调发病风险。我们最后讨论了未来研究的必要性，即描绘特定压力源对神经回路的影响，阐明海马体 - 隔区 - 下丘脑连接的相关性和功能，并研究关键神经肽如促肾上腺皮质激素释放激素（CRH）、催产素和胰高血糖素样肽 -1（GLP -1）在人类饮食失调发病机制中的作用。像单细胞测序和先进的人体成像等新兴工具可能会揭示饮食失调患者中与进食相关脑区的细胞和回路水平变化。最终，通过整合基础研究和临床研究，科学为开发针对饮食失调患者适应不良饮食行为的个性化、基于机制的治疗方法提供了有前景的途径。
