Miletta Maria Consolata, Horvath Tamas L
Larsson-Rosenquist Foundation Center for Neurodevelopment, Growth and Nutrition of the Newborn, Department of Neonatology, University of Zurich and University Hospital Zurich, 8006 Zurich, Switzerland.
Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Bio Protoc. 2023 Aug 5;13(15):e4730. doi: 10.21769/BioProtoc.4730.
Anorexia nervosa (AN) is a psychiatric disorder mainly characterized by extreme hypophagia, severe body weight loss, hyperactivity, and hypothermia. Currently, AN has the highest mortality rate among psychiatric illnesses. Despite decades of research, there is no effective cure for AN nor is there a clear understanding of its etiology. Since a complex interaction between genetic, environmental, social, and cultural factors underlines this disorder, the development of a suitable animal model has been difficult so far. Here, we present our protocol that couples a loss-of-function mouse model to the activity-based anorexia model (ABA), which involves self-imposed starvation in response to exposure to food restriction and exercise. We provide insights into a neural circuit that drives survival in AN and, in contrast to previous protocols, propose a model that mimics the conditions that mainly promote AN in humans, such as increased incidence during adolescence, onset preceded by negative energy balance, and increased compulsive exercise. This protocol will be useful for future studies that aim to identify neuronal populations or brain circuits that promote the onset or long-term maintenance of this devastating eating disorder.
神经性厌食症（AN）是一种精神疾病，主要特征为极度食欲不振、严重体重减轻、多动和体温过低。目前，AN在精神疾病中死亡率最高。尽管经过数十年研究，仍没有针对AN的有效治愈方法，对其病因也尚无清晰认识。由于遗传、环境、社会和文化因素之间的复杂相互作用构成了这种疾病的基础，到目前为止，开发合适的动物模型一直很困难。在此，我们展示我们的方案，该方案将功能丧失小鼠模型与基于活动的厌食模型（ABA）相结合，ABA涉及因接触食物限制和运动而自我施加饥饿。我们深入研究了驱动AN生存的神经回路，并且与先前的方案不同，提出了一个模拟主要在人类中促进AN的条件的模型，如青春期发病率增加、发病前能量负平衡以及强迫性运动增加。该方案将有助于未来旨在识别促进这种毁灭性饮食失调症发作或长期维持的神经元群体或脑回路的研究。
