清华大学姚骏团队的一项最新研究发现胰腺-海马反馈机制调节抑郁相关行为的昼夜节律变化。2025年8月11日出版的《自然—神经科学》杂志发表了这项成果。

本研究表明，来自双相情感障碍患者的诱导多能干细胞衍生的胰岛存在胰岛素分泌缺陷，这是由RORβ（一种双相情感障碍的易感基因）的表达增加引起的。增强无主题胰岛β细胞中RORβ的表达可诱导光期抑郁相关行为和暗期躁狂样行为。光照期胰腺RORβ过表达减少胰岛胰岛素释放，诱导海马过度活跃和抑郁样行为。

此外，这种海马在光明期的过度活跃对促进胰岛素在黑暗期的释放有延迟作用，导致躁狂样行为和海马神经元的低活性。他们在小鼠身上的研究结果表明，代谢和昼夜节律因素合作产生行为波动的胰腺-海马反馈机制可能在双相情感障碍中发挥作用。

据了解，神经精神障碍患者常表现出代谢症状。然而，这种共同发生的机制尚不清楚。

附：英文原文

Title: A pancreas–hippocampus feedback mechanism regulates circadian changes in depression-related behaviors

Author: Liu, Yao-Nan, Wang, Qiu-Wen, She, Xin-Yu, Li, Li-Jun, Wang, Bing, Yang, Ruilan, Li, Qian, Lu, Si-Yao, Wang, Ying-Han, Shen, Wei, Fu, Chong-Lei, Li, Dan, Yi, Lan, Wang, Chun-Xue, Shi, Wei, Cheng, Xin, Cao, Liping, Mi, Shuangli, Yao, Jun

Issue&Volume: 2025-08-11

Abstract: Individuals with neuropsychiatric disorders often show metabolic symptoms. However, the mechanisms underlying this co-occurrence remain unclear. Here we show that induced pluripotent stem cell-derived pancreatic islets from individuals with bipolar disorder have insulin secretion deficits caused by increased expression of RORβ, a susceptibility gene for bipolar disorder. Enhancing RORβ expression in mouse pancreatic β cells induced depression-related behaviors in the light phase and mania-like behaviors in the dark phase. Pancreatic RORβ overexpression in the light phase reduced insulin release from islets, inducing hippocampal hyperactivity and depression-like behaviors. Furthermore, this hippocampal hyperactivity in the light phase had the delayed effect of promoting insulin release in the dark phase, resulting in mania-like behaviors and hippocampal neuronal hypoactivity. Our results in mice point to a pancreas–hippocampus feedback mechanism by which metabolic and circadian factors cooperate to generate behavioral fluctuations and which may play a role in bipolar disorder.

DOI: 10.1038/s41593-025-02040-y

Source: https://www.nature.com/articles/s41593-025-02040-y