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The Journal of Headache and Pain
Published in: The Journal of Headache and Pain 1/2019

Open Access 01-12-2019 | Migraine | Research article

ROS/TRPA1/CGRP signaling mediates cortical spreading depression

Authors: Liwen Jiang, Dongqing Ma, Blair D. Grubb, Minyan Wang

Published in: The Journal of Headache and Pain | Issue 1/2019

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Abstract

Objectives

The transient receptor potential ankyrin A 1 (TRPA1) channel and calcitonin gene-related peptide (CGRP) are targets for migraine prophylaxis. This study aimed to understand their mechanisms in migraine by investigating the role of TRPA1 in cortical spreading depression (CSD) in vivo and exploring how reactive oxygen species (ROS)/TRPA1/CGRP interplay in regulating cortical susceptibility to CSD.

Methods

Immunohistochemistry was used for detecting TRPA1 expression. CSD was induced by K+ on the cerebral cortex, monitored using electrophysiology in rats, and intrinsic optical imaging in mouse brain slices, respectively. Drugs were perfused into contralateral ventricle of rats. Lipid peroxidation (malondialdehyde, MDA) analysis was used for indicating ROS level.

Results

TRPA1 was expressed in cortical neurons and astrocytes of rats and mice. TRPA1 deactivation by an anti-TRPA1 antibody reduced cortical susceptibility to CSD in rats and decreased ipsilateral MDA level induced by CSD. In mouse brain slices, H2O2 facilitated submaximal CSD induction, which disappeared by the antioxidant, tempol and the TRPA1 antagonist, A-967079; Consistently, TRPA1 activation reversed prolonged CSD latency and reduced magnitude by the antioxidant. Further, blockade of CGRP prolonged CSD latency, which was reversed by H2O2 and the TRPA1 agonist, allyl-isothiocyanate, respectively.

Conclusions

ROS/TRPA1/CGRP signaling plays a critical role in regulating cortical susceptibility to CSD. Inhibition ROS and deactivation of TRPA1 channels may have therapeutic benefits in preventing stress-triggered migraine via CGRP.
Literature
1.
2.
Pietrobon D, Moskowitz MA (2013) Pathophysiology of migraine. Annu Rev Physiol 75:365–391PubMed
3.
Lauritzen M (2001) Cortical spreading depression in migraine. Cephalalgia. 21(7):757–760PubMed
4.
Tepper SJ (2018) Anti-calcitonin gene-related peptide (CGRP) therapies: update on a previous review after the American headache society 60th scientific meeting, San Francisco, June 2018. Headache. 58(Suppl 3):276–290PubMed
5.
Jiang L, Wang Y, Xu Y, Ma D, Wang M (2018) The transient receptor potential ankyrin type 1 plays a critical role in cortical spreading depression. Neuroscience. 382:23–34PubMed
6.
Tozzi A, de Iure A, Di Filippo M, Costa C, Caproni S, Pisani A et al (2012) Critical role of calcitonin gene-related peptide receptors in cortical spreading depression. PNAS. 109(46):18985–18990PubMed
7.
Borkum JM (2016) Migraine triggers and oxidative stress: a narrative review and synthesis. Headache. 56(1):12–35PubMed
8.
Bernecker C, Ragginer C, Fauler G, Horejsi R, Moller R, Zelzer S et al (2011) Oxidative stress is associated with migraine and migraine-related metabolic risk in females. Eur J Neurol 18(10):1233–1239PubMed
9.
Geyik S, Altunisik E, Neyal AM, Taysi S (2016) Oxidative stress and DNA damage in patients with migraine. The journal of headache and pain. 17:10PubMedPubMedCentral
10.
Shatillo A, Koroleva K, Giniatullina R, Naumenko N, Slastnikova AA, Aliev RR et al (2013) Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system. Neuroscience. 253:341–349PubMed
11.
Malkov A, Ivanov AI, Popova I, Mukhtarov M, Gubkina O, Waseem T et al (2014) Reactive oxygen species initiate a metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression. J Cereb Blood Flow Metab 34(9):1540–1549PubMedPubMedCentral
12.
Yapici-Eser H, Donmez-Demir B, Kilic K, Eren-Kocak E, Dalkara T (2018) Stress modulates cortical excitability via alpha-2 adrenergic and glucocorticoid receptors: as assessed by spreading depression. Exp Neurol 307:45–51PubMed
13.
Zhang X, Levy D, Kainz V, Noseda R, Jakubowski M, Burstein R (2011) Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol 69(5):855–865PubMedPubMedCentral
14.
Zhang X, Levy D, Noseda R, Kainz V, Jakubowski M, Burstein R (2010) Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. J Neurosci 30(26):8807–8814PubMedPubMedCentral
15.
Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 112(6):819–829PubMed
16.
Kheradpezhouh E, Choy JMC, Daria VR, Arabzadeh E (2017) TRPA1 expression and its functional activation in rodent cortex. Open Biol 7(4)
17.
Julius D (2013) TRP channels and pain. Annu Rev Cell Dev Biol 29:355–384PubMed
18.
Kimura Y, Mikami Y, Osumi K, Tsugane M, Oka J, Kimura H (2013) Polysulfides are possible H2S-derived signaling molecules in rat brain. FASEB J 27(6):2451–2457PubMed
19.
Kim YS, Son JY, Kim TH, Paik SK, Dai Y, Noguchi K et al (2010) Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn. J Comp Neurol 518(5):687–698PubMed
20.
Demartini C, Tassorelli C, Zanaboni AM, Tonsi G, Francesconi O, Nativi C et al (2017) The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: evaluation in an animal model. J. Headache Pain 18(1):94PubMedPubMedCentral
21.
Marone IM, De Logu F, Nassini R, De Carvalho Goncalves M, Benemei S, Ferreira J et al (2018) TRPA1/NOX in the soma of trigeminal ganglion neurons mediates migraine-related pain of glyceryl trinitrate in mice. Brain. 141(8):2312–2328PubMedPubMedCentral
22.
Nassini R, Materazzi S, Vriens J, Prenen J, Benemei S, De Siena G et al (2012) The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. Brain. 135(Pt 2):376–390PubMed
23.
Bu F, Wang Y, Jiang L, Ma D, Quinn JP, Wang M (2017) Sarcoma family kinase activity is required for cortical spreading depression. Cephalalgia 38:1748–1758PubMed
24.
Bu F, Du R, Li Y, Quinn JP, Wang M (2016) NR2A contributes to genesis and propagation of cortical spreading depression in rats. Sci Rep 6(23679):1–9
25.
26.
Takizawa M, Harada K, Nakamura K, Tsuboi T (2018) Transient receptor potential ankyrin 1 channels are involved in spontaneous peptide hormone release from astrocytes. Biochem Biophys Res Commun 501(4):988–995PubMed
27.
Sullivan MN, Gonzales AL, Pires PW, Bruhl A, Leo MD, Li W et al (2015) Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. Sci Signal 8(358):ra2PubMedPubMedCentral
28.
Wang Y, Tye AE, Zhao J, Ma D, Raddant AC, Bu F et al (2016) Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression. Cephalalgia.
29.
Kunkler PE, Ballard CJ, Oxford GS, Hurley JH (2011) TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain. 152(1):38–44PubMed
30.
Dreier JP (2011) The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med 17(4):439–447PubMed
31.
Metadata
Title
ROS/TRPA1/CGRP signaling mediates cortical spreading depression
Authors
Liwen Jiang
Dongqing Ma
Blair D. Grubb
Minyan Wang
Publication date
01-12-2019
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2019
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-019-0978-z

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