Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model

• 成果类型: Article
• 署名作者: Rasmussen, Martin Kaag; Mollgard, Kjeld; Bork, Peter A. R.; Weikop, Pia; Esmail, Tina; Drici, Lylia; Albrechtsen, Nicolai J. Wewer; Carlsen, Jonathan Frederik; Huynh, Nguyen P. T.; Ghitani, Nima; Mann, Matthias; Goldman, Steven A.; Mori, Yuki; Chesler, Alexander T.; Nedergaard, Maiken
• 署名单位: University of Copenhagen; University of Copenhagen; University of Copenhagen; University of Copenhagen; University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; University of Rochester; Max Planck Society; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8530
• DOI: 10.1126/science.adl0544
• 发表日期: 2024-07-05
• 关键词: cortical spreading depression; blood-brain-barrier; peptide receptors; mass-spectrometry; aura; cgrp; sensitization; nociceptors; afferents; induction

摘要

Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and trigeminal cells. After CSD, similar to 11% of the CSF proteome is altered, with up-regulation of proteins that directly activate receptors in the trigeminal ganglion. CSF collected from animals exposed to CSD activates trigeminal neurons in naive mice in part by CSF-borne calcitonin gene-related peptide (CGRP). We identify a communication pathway between the central and peripheral nervous system that might explain the relationship between migrainous aura and headache.