1. Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model.
- Author
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Kaag Rasmussen M, Møllgård K, Bork PAR, Weikop P, Esmail T, Drici L, Wewer Albrechtsen NJ, Carlsen JF, Huynh NPT, Ghitani N, Mann M, Goldman SA, Mori Y, Chesler AT, and Nedergaard M
- Subjects
- Animals, Mice, Cerebrospinal Fluid metabolism, Disease Models, Animal, Proteome metabolism, Signal Transduction, Calcitonin Gene-Related Peptide cerebrospinal fluid, Calcitonin Gene-Related Peptide metabolism, Cortical Spreading Depression, Migraine Disorders cerebrospinal fluid, Migraine Disorders metabolism, Migraine Disorders physiopathology, Trigeminal Ganglion metabolism, Trigeminal Ganglion physiopathology
- Abstract
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, ~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 naïve 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.
- Published
- 2024
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