Cephalalgia : an international journal of headache · 2015
Temporal profiles of high-mobility group box 1 expression levels after cortical spreading depression in mice.
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Takizawa Tsubasa, Shibata Mamoru, Kayama Yohei, Toriumi Haruki, Ebine Taeko, Koh Anri, Shimizu Toshihiko, Suzuki Norihiro
Аннотация
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.
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.