Stress modulates cortical excitability via α-2 adrenergic and glucocorticoid receptors: As assessed by spreading depression

Yapici-Eser, Hale; Dönmez-Demir, Buket; Kılıç, Kıvılcım; Eren-Koçak, Emine; Dalkara, Turgay

doi:10.1016/j.expneurol.2018.05.024

Cited by 19 publications

(9 citation statements)

References 58 publications

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“…Interestingly, a recent work evaluated the effects of acute and chronic stress on CSD threshold in swiss albino mice. Similar to our work, this work showed that both acute and chronic stress did not change CSD frequency but did reduce CSD threshold ( Yapici-Eser et al, 2018 ). Even though our study used different mice and stress paradigms, it is possible that stressed mice might show a difference in CSD threshold but not frequency compared to controls.…”

Section: Discussionsupporting

confidence: 88%

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

Kaufmann

Brennan

2018

Front. Cell. Neurosci.

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Migraine is a disabling neurological disorder affecting 12% of the world’s population. Stress is a major reported trigger and exacerbator of migraine. We evaluated the effects of two chronic stress paradigms on migraine relevant phenotypes in male C57Bl/6 mice.Methods: Fifty six mice were used in a 14 day social defeat stress (SDS) and twenty three mice were used in a 40 day chronic variable stress (CVS) paradigm. Anxiety measures were evaluated using the open field and elevated plus maze (EPM) tests. Migraine relevant phenotypes were evaluated using the nitroglycerin (NTG) and cortical spreading depression (CSD) models.Results: Stress sensitive SDS mice and chronically stressed CVS mice showed decreased exploration in the open field and reduced time spent in the open arms of the EPM compared to controls. Stress sensitive and resilient SDS mice had increased serum corticosterone levels, and stressed mice in the CVS paradigm had decreased weight gain compared to controls, providing combined behavioral and physiological evidence of a stress response. In the CVS paradigm but not the SDS paradigm, the stressed group showed a significant decrease in baseline mechanical withdrawal threshold compared to controls. All groups showed a significant reduction in withdrawal threshold after treatment with NTG, but the reduction was not larger in SDS or CVS than in controls. Interestingly, stress resilient SDS mice showed a rapid recovery from NTG effects that was not seen in other groups. No difference in CSD frequency or velocity was seen between stress and control mice in either stress paradigms.Conclusion: We observed distinct effects of stress on generalized pain response, migraine relevant pain, and migraine relevant excitability. CVS but not SDS was associated with a reduced mechanical withdrawal threshold, consistent with a generalized pain response to chronic stress. Neither SDS nor CVS exacerbated phenotypes considered specifically relevant to migraine - withdrawal to NTG, and susceptibility to CSD. However, the significantly reduced response of stress resilient mice to the NTG stimulus may represent a specific migraine-resistant phenotype.

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Section: Discussionsupporting

confidence: 88%

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

Kaufmann

Brennan

2018

Front. Cell. Neurosci.

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“…Stress may increase cortical excitability by increasing extracellular glutamate or corticotropin-releasing hormone. In a study using Swiss albino mice, SD threshold was reduced by acute and chronic stress as well as by central noradrenergic denervation [93]. However, in another study in which 14-day social defeat stress and 40-day chronic variable stress were introduced to male C57Bl/6 mice, no difference in SD frequency or velocity was seen [94].…”

Section: Experimental Methods Of Sd Inductionmentioning

confidence: 99%

Spreading depression as a preclinical model of migraine

et al. 2019

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Spreading depression (SD) is a slowly propagating wave of near-complete depolarization of neurons and glial cells across the cortex. SD is thought to contribute to the underlying pathophysiology of migraine aura, and possibly also an intrinsic brain activity causing migraine headache. Experimental models of SD have recapitulated multiple migraine-related phenomena and are considered highly translational. In this review, we summarize conventional and novel methods to trigger SD, with specific focus on optogenetic methods. We outline physiological triggers that might affect SD susceptibility, review a multitude of physiological, biochemical, and behavioral consequences of SD, and elaborate their relevance to migraine pathophysiology. The possibility of constructing a recurrent episodic or chronic migraine model using SD is also discussed.

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“…Increased ROS is associated with migraine [8, 9] but also with CSD in the trigeminal nociceptive system [10]. This is supported by that the antioxidant, tempol, strongly reduces the CSD occurrence in vivo [11]; while the lowered-CSD threshold level is considered as stress-induced susceptibility to migraine [12]. Given that CSD activates trigeminovascular neurons and meningeal nociceptors [13, 14], molecules in the oxidative stress pathway that can modulate CSD are likely to be important targets in stress-related migraine.…”

Section: Introductionmentioning

confidence: 99%

ROS/TRPA1/CGRP signaling mediates cortical spreading depression

Jiang

Grubb

et al. 2019

J Headache Pain

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ObjectivesThe 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.MethodsImmunohistochemistry 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.ResultsTRPA1 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.ConclusionsROS/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.

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Stress modulates cortical excitability via α-2 adrenergic and glucocorticoid receptors: As assessed by spreading depression

Cited by 19 publications

References 58 publications

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

Spreading depression as a preclinical model of migraine

ROS/TRPA1/CGRP signaling mediates cortical spreading depression

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