远距离胆碱能输入促进胶质母细胞瘤的进展，这一成果由第三军医大学陈图南研究小组经过不懈努力而取得。该研究于2025年8月18日发表于国际一流学术期刊《癌细胞》杂志上。

通过单突触狂犬病追踪，该课题组研究人员将全脑神经输入映射到患者来源的异种移植物，并揭示了一致的组织逻辑：局部输入主要是谷氨酸，而远程连接表现出不同的神经递质谱，基底前脑胆碱能投射作为跨部位的保守输入出现。功能上，突触前乙酰胆碱释放通过毒蕈碱受体CHRM3以电路特异性方式促进GBM进展。从机制上讲，谷氨酸能和胆碱能信号聚集在一起增强胶质瘤钙瞬态，但在时间转录控制上存在分歧，它们的双重阻断产生叠加的抗肿瘤作用。在治疗上，抗胆碱能药物东莨菪碱能减缓胶质瘤的生长，而乙酰胆碱酯酶抑制剂多奈哌齐则会加重疾病。这些发现揭示了神经元-胶质瘤连接的复杂性，强调了远距离神经调节通路是GBM有希望的治疗靶点。

据了解，胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，其形成与神经网络的整合。虽然谷氨酸能输入与肿瘤进展有关，但神经胶质瘤连接体的更广泛的结构和功能尚不清楚。

附：英文原文

Title: Long-range cholinergic input promotes glioblastoma progression

Author: Yang Yang, Chuanyan Yang, Xuezhu Chen, Yibin Jiang, Xuejiao Lei, Kang Ma, Yulian Quan, Tianran Li, Chenfu Guo, Yijing Meng, Lin Kang, Xinyu Zhang, Long Jin, Jiafeng Huang, Ning Mu, Zexuan Yan, Qinghua Ma, Shuai Wang, Yanxia Wang, Yong-Ning Shang, Cong Chen, Yu Shi, Shukun Hu, Likun Yang, Chuan Lan, Rong Hu, Ying Zhang, Xia Li, Yunqing Li, Chong Liu, Yu-Hai Wang, Fei Li, Hua Feng, Xiu-Wu Bian, Tunan Chen

Issue&Volume: 2025-08-18

Abstract: Glioblastoma (GBM), the most aggressive primary brain tumor, is shaped by its integration into neural networks. While glutamatergic input is linked to tumor progression, the broader architecture and function of neuron-glioma connectomes remain unclear. Using monosynaptic rabies tracing, we map brain-wide neural input to patient-derived xenografts and reveal a consistent organizational logic: local inputs are primarily glutamatergic, while long-range connections exhibit diverse neurotransmitter profiles, with basal forebrain cholinergic projections emerging as a conserved input across sites. Functionally, presynaptic acetylcholine release promotes GBM progression through muscarinic receptor CHRM3 in a circuit-specific manner. Mechanistically, glutamatergic and cholinergic signals converge to enhance glioma calcium transients but diverge in temporal transcriptional control, with their dual blockade producing additive anti-tumor effects. Therapeutically, the anticholinergic drug scopolamine attenuates glioma growth, whereas the acetylcholinesterase inhibitor donepezil exacerbates disease. These findings reveal the complexity of neuron-glioma connectivity, highlighting long-range neuromodulatory pathways as promising therapeutic targets in GBM.

DOI: 10.1016/j.ccell.2025.07.024

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00330-7