查找使用阿拉丁产品的科研文献

Long-range cholinergic input promotes glioblastoma progression

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

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.