Publication Date:
2013-03-02
Description:
The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1 activation followed by high-mobility group box 1 (HMGB1) release from neurons and nuclear factor kappaB activation in astrocytes. Suppression of this cascade abolished CSD-induced trigeminovascular activation, dural mast cell degranulation, and headache. CSD-induced neuronal megachannel opening may promote sustained activation of trigeminal afferents via parenchymal inflammatory cascades reaching glia limitans. This pathway may function to alarm an organism with headache when neurons are stressed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karatas, Hulya -- Erdener, Sefik Evren -- Gursoy-Ozdemir, Yasemin -- Lule, Sevda -- Eren-Kocak, Emine -- Sen, Zumrut Duygu -- Dalkara, Turgay -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1092-5. doi: 10.1126/science.1231897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449592" target="_blank"〉PubMed〈/a〉
Keywords:
Afferent Pathways
;
Animals
;
Astrocytes/metabolism/physiology
;
Caspase 1/metabolism
;
Connexins/antagonists & inhibitors/*biosynthesis
;
*Cortical Spreading Depression
;
HMGB1 Protein/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Migraine Disorders/metabolism/*physiopathology
;
NF-kappa B/metabolism
;
Nerve Fibers/physiology
;
Nerve Tissue Proteins/antagonists & inhibitors/*biosynthesis
;
Neurons/metabolism/*physiology
;
Protein Transport
;
Signal Transduction
;
Trigeminal Nerve/metabolism/*physiopathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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