Zeng Qiuting, Shan Weiran, Zhang Hui, Yang Jianjun, Zuo Zhiyi
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, U.S.A.
Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Theranostics. 2021 Feb 6;11(8):3813-3829. doi: 10.7150/thno.45690. eCollection 2021.
Consolation behaviors toward the sick are common in humans. Anxiety in the relatives of the sick is also common. Anxiety can cause detrimental effects on multiple systems. However, our understanding on the neural mechanisms of these behaviors is limited because of the lack of small animal models. Five of 6- to 8-week-old CD-1 male mice were housed in a cage. Among them, 2 mice had right common artery exposure (surgery) and the rest were without surgery. Allo-grooming and performance in light and dark box and elevated plus maze tests of the mice were determined. Mice without surgery had increased allo-grooming toward mice with surgery but decreased allo-grooming toward non-surgery intruders. This increased allo-grooming toward surgery mice was higher in familiar observers of surgery mice than that of mice that were not cage-mates of surgery mice before the surgery. Familiar observers developed anxious behavior after being with surgery mice. Surgery mice with familiar observers had less anxious behavior than surgery mice without interacting with familiar observers. Multiple brain regions including paraventricular thalamic nucleus (PVT) were activated in familiar observers. The activated cells in PVT contained orexin receptors. Injuring the neurons with ibotenic acid, antagonizing orexin signaling with an anti-orexin antibody or inhibiting neurons by chemogenetic approach in PVT abolished the consolation and anxious behaviors of familiar observers. Mice show consolation behavior toward the sick. This behavior attenuates the anxious behavior of surgery mice. The orexin signaling in the PVT neurons play a critical role in the consolation of familiar observers toward surgery mice and their anxious behavior. Considering that about 50 million patients have surgery annually in the United States, our study represents the initial attempt to understand neural mechanisms for consolation and anxiety of a large number of people.
对生病个体的安慰行为在人类中很常见。病人亲属的焦虑也很常见。焦虑会对多个系统产生有害影响。然而,由于缺乏小动物模型,我们对这些行为的神经机制的了解有限。将6至8周龄的CD-1雄性小鼠6只中的5只饲养在一个笼子里。其中,2只小鼠进行了右颈总动脉暴露(手术),其余未进行手术。测定了小鼠的异体梳理行为以及在明暗箱和高架十字迷宫试验中的表现。未手术的小鼠对手术小鼠的异体梳理行为增加,但对未手术的入侵者的异体梳理行为减少。对手术小鼠的这种增加的异体梳理行为,手术小鼠的熟悉观察者比手术前不是同笼伙伴的小鼠更高。熟悉的观察者在与手术小鼠在一起后出现了焦虑行为。有熟悉观察者的手术小鼠比未与熟悉观察者互动的手术小鼠焦虑行为更少。包括室旁丘脑核(PVT)在内的多个脑区在熟悉的观察者中被激活。PVT中被激活的细胞含有食欲素受体。用鹅膏蕈氨酸损伤神经元、用抗食欲素抗体拮抗食欲素信号或通过化学遗传学方法抑制PVT中的神经元,消除了熟悉观察者的安慰和焦虑行为。小鼠对生病个体表现出安慰行为。这种行为减轻了手术小鼠的焦虑行为。PVT神经元中的食欲素信号在熟悉的观察者对手术小鼠的安慰及其焦虑行为中起关键作用。考虑到美国每年约有5000万患者接受手术,我们的研究代表了对大量人群安慰和焦虑神经机制的初步探索。