胶质母细胞瘤重塑人类神经回路降低了存活率。神经癌症正反馈。加巴喷丁阻神经脉冲抑神经癌症。本文是神经癌症发病机理关联基础医学研究论文。
(Translated by Baidu: )
Brain thinking promotes the growth of nerve tumors? Nature Research Reveals the Mechanism of Glioblastoma Remodeling Neural circuit
Glioblastoma remodeling of the human Neural circuit reduces survival. Neurocancer positive feedback. Gabapentin blocks nerves and channels and suppresses nerve cancer. This is a research paper on the pathogenesis of neural cancer related to Medicine#Basic sciences.
（百度翻訳： ）
脳の思考が神経腫瘍の成長を促進する？Nature研究により、膠質母細胞腫による神経回路の再形成メカニズムが明らかになった
膠質母細胞腫によるヒト神経回路の再形成は生存率を低下させた。神経癌はフィードバックしている。ガバペンチンは神経パルスを阻害して神経癌を抑制する。本文は神経癌発病機序関連基礎医学研究論文である。
BioArt
2023/06/12
论文
论文标题：Glioblastoma remodelling of human neural circuits decreases survival
作者：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.
期刊：Nature
发表时间：2023/05/03
数字识别码：10.1038/s41586-023-06036-1
摘要：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.
2023年5月3日，来自加州大学旧金山分校的Shawn L. Hervey-Jumper团队在Nature杂志上发表了文章 Glioblastoma remodelling of human neural circuits decreases survival ，他们在患者进行语言任务测试时进行了电生理研究，并对特定部位进行肿瘤组织活检，证明神经胶质瘤会重塑功能性神经回路，其与正常大脑之间的功能连接程度会对患者的生存和语言任务的表现产生负面影响。
虽然已知胶质母细胞瘤浸润脑内的神经元在静息时过度兴奋，但在特定任务情境下神经元过度兴奋的程度仍不清楚。为此，作者对一组在外侧前额叶皮层（lateral prefrontal cortex, LPFC）发生肿瘤浸润的成年患者在认知任务情境下进行电生理研究。电极分别放置在肿瘤浸润和正常皮质上，HGp（high-gamma band range power）数据显示两个位置的频率明显分离，浸润部位在语言产生过程中HGp明显增加，表现出过度兴奋（图1）。研究者使用脑磁图 (MEG) 检测胶质瘤浸润脑内的神经元振荡并对手术肿瘤切除过程中胶质瘤内的功能连接区域采样并进行RNA-seq分析，发现大量参与神经回路组装的基因在高功能连接（HFC）肿瘤区域内上调，尤其是编码参与突触形成的血小板反应素-1（TSP-1）发生7倍的上调，且与低功能连接（LFC）区域相比，HFC区域内的突触标记（Synapsin和PSD-95）增加，提示胶质母细胞瘤HFC区域的突触稳定性和形成增加，支持TSP-1在胶质瘤相关神经回路重塑中的作用。
1. Venkatesh, H. S. et al. Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma. Nature 549, 533–537 (2017).
2. Campbell, S. L., Buckingham, S. C. & Sontheimer, H. Human glioma cells induce hyperexcitability in cortical networks. Epilepsia 53, 1360–1370 (2012).
3. Campbell, S. L. et al. GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor-associated epilepsy. Glia 63, 23–36 (2015).
