Temporal profiles of high-mobility group box 1 expression levels after cortical spreading depression in mice. (January 2016)

• Record Type: Journal Article
• Authors: Takizawa, Tsubasa; Shibata, Mamoru; Kayama, Yohei; Toriumi, Haruki; Ebine, Taeko; Koh, Anri; Shimizu, Toshihiko; Suzuki, Norihiro
• Is Part Of: Cephalalgia. Volume 36:Number 1(2016)
• Page Start: 44
• Page End: 52
• Publication Date: 2016-01
• Subjects: Cortical spreading depression -- high-mobility group box 1 -- neuron -- astrocyte -- transcriptional activity; Headache -- Periodicals; 616.8491
• DOI: 10.1177/0333102415580100
• Languages: English
• ISSNs: 0333-1024

Abstract

Introduction: Cortical spreading depression (CSD) has recently been shown to induce the release of the nuclear protein termed high-mobility group box 1 from neurons, causing activation of the trigeminovascular system. Here, we explored the effects of single and multiple cortical spreading depression inductions on high-mobility group box 1 (HMGB1) transcriptional activity relative to high-mobility group box 1 protein expression levels and intracellular localization in cortical neurons and astrocytes. Methods: Single or multiple cortical spreading depression inductions were achieved by KCl application to the mouse cerebral cortex. The animals were sacrificed at 30 minutes, 3 hours and 24 hours after cortical spreading depression induction. High-mobility group box 1 expression levels were explored with in situ hybridization, Western blotting and immunostaining. Results: Cortical spreading depression up-regulated high-mobility group box 1 transcriptional activity in neurons at 3 hours in a manner that was dependent on the number of cortical spreading depression inductions. At 24 hours, the high-mobility group box 1 transcriptional activity had returned to basal levels. Cortical spreading depression induced a reduction in high-mobility group box 1 protein expression at 3 hours, which was also dependent on the number of cortical spreading depression inductions. Following cortical spreading depression, the release of high-mobility group box 1 from the nucleus was observed in a small proportion of neurons, but not in astrocytes. Conclusion: Cortical spreading depression induced translocation of high-mobility group box 1 from neuronal nuclei, driving transcriptional up-regulation of high-mobility group box 1 to maintain protein levels.