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

Martin Kaag Rasmussen; Kjeld Møllgård; Peter A R Bork; Pia Weikop; Tina Esmail; Lylia Drici; Nicolai J Wewer Albrechtsen; Jonathan Frederik Carlsen; Nguyen P T Huynh; Nima Ghitani; Matthias Mann; Steven A Goldman; Yuki Mori; Alexander T Chesler; Maiken Nedergaard

doi:10.1126/science.adl0544

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

Martin Kaag Rasmussen, Kjeld Møllgård, Peter A R Bork, Pia Weikop, Tina Esmail, Lylia Drici, Nicolai J Wewer Albrechtsen, Jonathan Frederik Carlsen, Nguyen P T Huynh, Nima Ghitani, Matthias Mann, Steven A Goldman, Yuki Mori, Alexander T Chesler, Maiken Nedergaard^*

^*Corresponding author for this work

51 Citations (Scopus)

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.

Original language	English
Journal	Science (New York, N.Y.)
Volume	385
Issue number	6704
Pages (from-to)	80-86
Number of pages	7
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.adl0544
Publication status	Published - 5 Jul 2024

Keywords

Animals
Trigeminal Ganglion/metabolism
Mice
Calcitonin Gene-Related Peptide/cerebrospinal fluid
Migraine Disorders/cerebrospinal fluid
Disease Models, Animal
Cortical Spreading Depression
Cerebrospinal Fluid/metabolism
Mice, Inbred C57BL
Male
Proteome/metabolism
Signal Transduction

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Kaag Rasmussen, M., Møllgård, K., Bork, P. A. R., Weikop, P., Esmail, T., Drici, L., Wewer Albrechtsen, N. J., Carlsen, J. F., Huynh, N. P. T., Ghitani, N., Mann, M., Goldman, S. A., Mori, Y., Chesler, A. T., & Nedergaard, M. (2024). Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model. Science (New York, N.Y.), 385(6704), 80-86. https://doi.org/10.1126/science.adl0544

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 & Nedergaard, M 2024, 'Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model', Science (New York, N.Y.), vol. 385, no. 6704, pp. 80-86. https://doi.org/10.1126/science.adl0544

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title = "Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model",

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, \textasciitilde{}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 na{\"i}ve 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.",

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volume = "385",

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AU - Kaag Rasmussen, Martin

AU - Møllgård, Kjeld

AU - Bork, Peter A R

AU - Weikop, Pia

AU - Esmail, Tina

AU - Drici, Lylia

AU - Wewer Albrechtsen, Nicolai J

AU - Carlsen, Jonathan Frederik

AU - Huynh, Nguyen P T

AU - Ghitani, Nima

AU - Mann, Matthias

AU - Goldman, Steven A

AU - Mori, Yuki

AU - Chesler, Alexander T

AU - Nedergaard, Maiken

PY - 2024/7/5

Y1 - 2024/7/5

N2 - 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.

AB - 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.

KW - Animals

KW - Trigeminal Ganglion/metabolism

KW - Mice

KW - Calcitonin Gene-Related Peptide/cerebrospinal fluid

KW - Migraine Disorders/cerebrospinal fluid

KW - Disease Models, Animal

KW - Cortical Spreading Depression

KW - Cerebrospinal Fluid/metabolism

KW - Mice, Inbred C57BL

KW - Male

KW - Proteome/metabolism

KW - Signal Transduction

UR - https://www.scopus.com/pages/publications/85197805625

U2 - 10.1126/science.adl0544

DO - 10.1126/science.adl0544

M3 - Journal article

C2 - 38963846

SN - 0036-8075

VL - 385

SP - 80

EP - 86

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6704

ER -

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

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