近日，美国华盛顿大学医学院
该团队通过靶向关键回路节点来缓解这些冷漠样症状：给予抗IL-6抗体治疗，消除脑干细胞因子感知，光遗传学或药理学提高中脑边缘多巴胺。他们的发现揭示了一个感知全身炎症并协调行为变化的中枢神经回路，为慢性炎症和抑郁症状之间的联系提供了机制上的见解。
据介绍，恶病质是一种与炎症相关的严重消耗综合征，常导致多器官衰竭和死亡。恶病质患者会经历极度疲劳、冷漠和临床抑郁，然而这些行为症状背后的生物学机制及其与疾病的关系尚不清楚。在一个单主题癌症模型中，恶病质通过细胞因子感知脑干-基底神经节回路特异性地诱导了努力敏感性和冷漠样症状的增加。这种神经回路在恶病质发作时检测到白细胞介素-6 （IL-6）升高，并将炎症信号转化为中脑边缘多巴胺减少，从而增加努力敏感性。
附：英文原文
Title: A neuroimmune circuit mediates cancer cachexia-associated apathy
Author: Sarah Starosta, Miriam Ferrer, Quentin Chevy, Federica Lucantonio, Rodrigo Muoz-Castaeda, Francesca R. Fiocchi, Mason Bergstrom, Aubrey A. Siebels, Thomas Upin, Michael Wulf, Sarah Evans, Alexxai V. Kravitz, Pavel Osten, Tobias Janowitz, Marco Pignatelli, Adam Kepecs
Issue&Volume: 2025-04-11
Abstract: Cachexia, a severe wasting syndrome associated with inflammatory conditions, often leads to multiorgan failure and death. Patients with cachexia experience extreme fatigue, apathy, and clinical depression, yet the biological mechanisms underlying these behavioral symptoms and their relationship to the disease remain unclear. In a mouse cancer model, cachexia specifically induced increased effort-sensitivity, apathy-like symptoms through a cytokine-sensing brainstem-to-basal ganglia circuit. This neural circuit detects elevated interleukin-6 (IL-6) at cachexia onset and translates inflammatory signals into decreased mesolimbic dopamine, thereby increasing effort sensitivity. We alleviated these apathy-like symptoms by targeting key circuit nodes: administering an anti–IL-6 antibody treatment, ablating cytokine sensing in the brainstem, and optogenetically or pharmacologically boosting mesolimbic dopamine. Our findings uncovered a central neural circuit that senses systemic inflammation and orchestrates behavioral changes, providing mechanistic insights into the connection between chronic inflammation and depressive symptoms.
DOI: adm8857
Source: https://www.science.org/doi/10.1126/science.adm8857