Liu Haiying, Huang Xin, Xia Ruixin, Zhao Xin, Li Zimeng, Liu Qian, Li Congye, Mao Honghui, Wang Wenting, Wu Shengxi
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
Departments of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Neurosci Bull. 2025 Mar 15. doi: 10.1007/s12264-025-01384-6.
Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
正常的心脏功能依赖于大脑的复杂调控，而脑-心轴的异常会影响多种疾病，如心肌梗死和焦虑症。然而，目前缺乏对与心脏输入和输出相关的脑区进行系统追踪。在本研究中，我们将逆行跨突触伪狂犬病病毒（PRV）和顺行跨突触单纯疱疹病毒（HSV）注入小鼠左心室壁，以确定与心脏输入和输出相关的全脑区域。我们在雄性和雌性小鼠的至少170个脑亚区成功检测到PRV和HSV表达。性别差异主要发现于下丘脑和延髓，雄性小鼠比雌性小鼠表现出更强的相关性和层次聚类，表明雄性小鼠病毒表达模式的相似性降低和模块化增加。对不同注射时间线的进一步图论和多元线性回归分析显示，PRV的枢纽区域具有高度相似的簇，分布在不同脑区水平，提示心脏存在自上而下、层次传递的神经控制模式。HSV的枢纽区域有分散的簇，脑区集中在皮层和脑干，提示心脏存在自下而上、跨越式、多点神经传感模式。这两种模式都包含许多在脑-心轴研究中先前被忽视的枢纽脑区。这些结果为未来研究提供了脑靶点，并将有助于更深入地了解特定心脏疾病所涉及的脑机制。
