2022
DOI: 10.1101/2022.09.26.509535
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The Effect of P2X7 Antagonism on Subcortical Spread of Optogenetically-Triggered Cortical Spreading Depression and Neuroinflammation

Abstract: Migraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in the opening of pannexin-1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and … Show more

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Cited by 1 publication
(6 citation statements)
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“…Interestingly, a recent finding shows that NF-κB p65 coexpresses with P2X7 receptor in mice cortical and subcortical structures. In this study, the authors report that optogenetically-triggered CSD induces NF-κB p65 nuclear translocation, which can be reversed by a P2X7 receptor antagonist [49]. Consistently, Fyn kinase activity also enhances NF-κB p65 nuclear translocation, which correlates with IL-1β gene expression in a Parkinson's disease model [50].…”
Section: Discussionmentioning
confidence: 58%
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“…Interestingly, a recent finding shows that NF-κB p65 coexpresses with P2X7 receptor in mice cortical and subcortical structures. In this study, the authors report that optogenetically-triggered CSD induces NF-κB p65 nuclear translocation, which can be reversed by a P2X7 receptor antagonist [49]. Consistently, Fyn kinase activity also enhances NF-κB p65 nuclear translocation, which correlates with IL-1β gene expression in a Parkinson's disease model [50].…”
Section: Discussionmentioning
confidence: 58%
“…These data imply that Fyn-dependent NMDA receptor activity is required for mediating CSD susceptibility. Unlike disrupting the NMDA receptor-Fyn interaction, disrupting the NMDA receptor-Src interaction by TAT-Src (40)(41)(42)(43)(44)(45)(46)(47)(48)(49) does not affect CSD (Fig. 5c, d).…”
Section: Discussionmentioning
confidence: 94%
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