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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (11): 1453-1466.doi: 10.12092/j.issn.1009-2501.2025.11.002

• 食欲素及其受体阻断剂治疗失眠障碍研究进展 • 上一篇    下一篇

超越睡眠觉醒调控:食欲素调控认知与情绪功能研究进展

李亚东1,2,于清崧1,何超3,王静1   

  1. 1上海交通大学医学院松江研究院,上海市情感脑功能与障碍干预重点实验室,上海交通大学医学院附属松江医院消化内科,上海  201699;2 上海交通大学护理学院,上海  200240;3 陆军军医大学(第三军医大学)基础医学院生理学教研室,重庆  400038
  • 出版日期:2025-11-26 发布日期:2025-12-04
  • 通讯作者: 李亚东,博士,上海交通大学医学院研究员,博士生导师。课题组研究睡眠觉醒对认知情感行为的调控作用及神经机制:发现乳头上核脑区为核心的觉醒系统支撑记忆和情感的生理作用;揭示了前扣带回皮层调控慢性痛失眠的病理机制;并为干预睡眠觉醒系统改善阿尔茨海默病认知情感障碍提供了新策略。相关研究成果发表在Nature Neuroscience,Cell Stem Cell和Neuron等杂志。获得国家级和上海市人才项目资助,美国脑与行为基金会(BBRF)青年科学家,主持科技部重点研发计划和科技创新2030重大项目课题。 E-mail:yadlee@sjtu.edu.cn;wangj0081@126.com
  • 基金资助:
    科技部重点研发计划(2025YFE0108000),科技创新2030重大项目(2025ZD0215000),国家自然科学基金(32371028,U24A20373),上海市科技创新行动计划启明星项目(24QA2704800),“上海交通大学2030”项目

Beyond sleep-wake regulation: roles of orexin in cognition and emotion regulation

LI Yadong1, 2, YU Qingsong1, HE Chao3, WANG Jing1   

  1. 1Songjiang Research Institute, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Emotional Brain Function and Intervention for Brain Disorders; Department of Gastroenterology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201699, China; 2 School of Nursing, Shanghai Jiao Tong University, Shanghai 200240, China; 3 Department of Physiology, College of Basic Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China

  • Online:2025-11-26 Published:2025-12-04

摘要:

食欲素(又称下丘脑分泌素)是调控睡眠-觉醒的重要神经递质。然而,日益增多的证据表明,食欲素能系统在认知与情感等高级脑功能调控中也同样扮演者核心角色,但相关作用机制缺乏系统性总结。本综述旨在填补此空白:首先,我们梳理食欲素能系统在生理状态下调控认知与情感的神经环路及分子机制;继而,重点探讨在衰老与神经退行性疾病中,该系统受损导致认知与情感障碍的病理机制;最后,基于上述机制,展望以食欲素能系统为靶点改善认知、情绪功能的药物研发前景。我们提出核心观点:通过靶向食欲素能系统提高觉醒水平,是改善认知与情绪功能的关键途径。本综述将深化对食欲素能系统功能多样性的理解,并丰富“觉醒-认知”调控的理论体系。 

关键词: 神经退行性疾病, 情绪, 记忆, 受体药物, 神经环路, 阿尔茨海默病

Abstract:

Orexin, also known as hypocretin, is a neuropeptide crucial for the regulation of sleep–wake states. Emerging evidence indicates that the orexinergic system also plays a pivotal role in cognitive and emotional functions, yet a comprehensive synthesis of these findings is lacking. In this review, we first summarize the neurocircuitry and molecular mechanisms by which the orexinergic system regulates cognition and emotion under physiological conditions. We then focus on how dysfunction of the orexinergic system contributes to cognitive and affective impairments in aging and neurodegenerative diseases. Finally, we discuss the therapeutic potential of targeting the orexinergic system to enhance cognitive and emotional function. We propose that modulating orexinergic system to increase arousal levels represents a key strategy for improving cognition and emotion. Advancing research in this area will deepen our understanding of orexin function and enrich theoretical frameworks linking arousal, cognition, and emotion.

Key words: neurodegenerative diseases, emotion, memory, receptor-based therapeutics, neuronal circuits, Alzheimer's disease

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