小柯机器人

美国加州大学旧金山分校Shawn L. Hervey-Jumper团队发现，胶质母细胞瘤对人类神经回路的重塑会降低生存率。该项研究成果发表在2023年5月3日出版的《自然》上。

研究人员试图确定胶质瘤引起的神经元变化如何影响认知的神经回路，以及这些相互作用是否影响病人的生存。通过对清醒人进行词汇检索语言任务时的颅内脑记录，以及特定部位的肿瘤组织活检和细胞生物学实验，研究人员发现胶质瘤重塑了功能性神经回路，从而使任务相关的神经反应激活了肿瘤浸润的皮层，远远超出了健康大脑中通常被招募的皮层区域。从肿瘤内表现出肿瘤和大脑其他部分之间高度功能连接的区域进行定点活检，富含胶质母细胞瘤亚群，表现出独特的突触源和神经元营养表型。

来自功能连接区域的肿瘤细胞会分泌突触因子thrombospondin-1，这有助于在功能连接的肿瘤区域与功能连接较少的肿瘤区域相比观察到不同的神经元-胶质瘤相互作用。使用FDA批准的药物加巴喷丁对thrombospondin-1进行药理抑制，可减少胶质母细胞瘤的增殖。胶质母细胞瘤和正常大脑之间的功能连接程度对病人的生存和语言任务的表现都有负面影响。这些数据表明，高级别胶质瘤在功能上重塑了人类大脑的神经回路，这既促进了肿瘤的发展，也损害了认知能力。

据悉，胶质瘤通过突触融入神经回路。以前的研究已经证明了神经元和胶质瘤细胞之间的双向互动，神经元活动驱动胶质瘤生长，胶质瘤增加神经元的兴奋性。

附：英文原文

Title: Glioblastoma remodelling of human neural circuits decreases survival

Author: Krishna, Saritha, Choudhury, Abrar, Keough, Michael B., Seo, Kyounghee, Ni, Lijun, Kakaizada, Sofia, Lee, Anthony, Aabedi, Alexander, Popova, Galina, Lipkin, Benjamin, Cao, Caroline, Nava Gonzales, Cesar, Sudharshan, Rasika, Egladyous, Andrew, Almeida, Nyle, Zhang, Yalan, Molinaro, Annette M., Venkatesh, Humsa S., Daniel, Andy G. S., Shamardani, Kiarash, Hyer, Jeanette, Chang, Edward F., Findlay, Anne, Phillips, Joanna J., Nagarajan, Srikantan, Raleigh, David R., Brang, David, Monje, Michelle, Hervey-Jumper, Shawn L.

Issue&Volume: 2023-05-03

Abstract: Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1,2,3,4 and gliomas increasing neuronal excitability2,5,6,7,8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron–glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

DOI: 10.1038/s41586-023-06036-1

Source: https://www.nature.com/articles/s41586-023-06036-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html