Intercellular communication in the brain through a dendritic nanotubular network

• 成果类型: Article
• 署名作者: Chang, Minhyeok; Krussel, Sarah; Parajuli, Laxmi Kumar; Kim, Juhyun; Lee, Daniel; Merodio, Alec; Kwon, Jaeyoung; Okabe, Shigeo; Kwon, Hyung-Bae
• 署名单位: Johns Hopkins University; Johns Hopkins Medicine; University of Tokyo; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Ruprecht Karls University Heidelberg; University of Freiburg; Korea Brain Research Institute (KBRI)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adr7403
• 发表日期: 2025-10-02
• 页码: eadr7403
• 关键词: FIBRILLAR ALPHA-SYNUCLEIN; amyloid-beta; TUNNELING NANOTUBES; pathology; protein; cytonemes; neurons; ORGANIZATION; TRAFFICKING; inhibition

摘要

Intercellular nanotubular networks mediate material exchange, but their existence in neurons remains to be explored in detail. We identified long, thin dendritic filopodia forming direct dendrite-dendrite nanotubes (DNTs) in mammalian cortex. Super-resolution microscopy in dissociated neurons revealed DNTs' actin-rich composition and dynamics, enabling long-range calcium ion (Ca2+) propagation. Imaging and machine learning-based analysis validated in situ DNTs as anatomically distinct from synaptic spines. DNTs actively transported small molecules and human amyloid-beta (A beta); DNT density increased before plaque formation in the medial prefrontal cortex of APP/PS1 mice (APP, A beta precursor protein; PS1, presenilin-1), suggesting that the dendrite-DNT network might play a role in Alzheimer's disease pathology. Computational models of DNT-mediated A beta propagation recapitulated early amyloidosis, predicting selective intracellular accumulation. These findings uncover a nanotubular connectivity layer in the brain, extending neuronal communication beyond classical synapses.