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. 2011 Oct;31(7):1071-8.
doi: 10.1007/s10571-011-9706-1. Epub 2011 May 20.

p65/RelA-Ser529 NF-κB subunit phosphorylation induces autophagic astroglial death (Clasmatodendrosis) following status epilepticus

Affiliations

p65/RelA-Ser529 NF-κB subunit phosphorylation induces autophagic astroglial death (Clasmatodendrosis) following status epilepticus

Hea Jin Ryu et al. Cell Mol Neurobiol. 2011 Oct.

Abstract

Clasmatodendrosis is an irreversible astroglial degenerative change, which includes extensive swelling and vacuolization of cell bodies and disintegrated and beaded processes. This study was designed to elucidate whether clasmatodendrosis may be one of the autophagy-related degeneration of astrocytes. In this study, clasmatodendritic astrocytes were observed only in the stratum radiatum in the CA1 region. Vacuoles in clasmatodendritic astrocytes showed LAMP-1 immunoreactivity. In addition, both LC3-II and Beclin-1 expression were detected in most of clasmatodendritic astrocytes as well as a few non-vacuolized astrocytes. Clasmatodendritic astrocytes also showed p65/RelA-Ser529 phosphorylation in the nuclei. The neutralization of TNF-α by sTNFp55R infusion reduced clasmatodendritic astrocytes with nuclear p65/RelA-Ser529 phosphorylation. Therefore, these findings suggest that clasmatodendrosis may be autophagic astroglial death in response to epileptic seizures through TNF-α-mediated p65/RelA-Ser529 phosphorylation.

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Figures

Fig. 1
Fig. 1
Clasmatodendorosis is autophagic astroglial death. (a) Vacuoles in clasmatodendritic astrocytes show LAMP-1 immunoreactivity (arrows). (b) Vacuoles in clasmatodendritic astrocytes do not contain EEA-1 immunoreactivity (arrowheads). (c) Beclin-1 immunoreactivity is observed in the cytoplasm of clasmatodenritic astrocytes (arrows). (d) Vacuoles in clasmatodendritic astrocytes show LC3-II immunoreactivity (arrows). Bar = 12.5 μm
Fig. 2
Fig. 2
p65/RelA NF-κB phosphorylation and TNFp75 receptor expression in clasmatodendritic astrocytes. (a) p65/RelA-Ser276 NF-κB phosphorylation. (b) p65/RelA-Ser311 NF-κB phosphorylation. (c) p65/RelA-Ser529 NF-κB phosphorylation. Only p65/RelA-Ser529 NF-κB phosphorylation is observed in the watery nucleus of clasmatodendritic astrocytes (arrow). (d) TNFp75 receptor expression in clasmatodendritic astrocytes (arrows). Bar = 5 (c) and 10 (a, b, and d) μm
Fig. 3
Fig. 3
Effect of sTNFp55R infusion on clasmatodendrosis (a, b). As compared with saline-infusion (a, arrows), sTNFp55R infusion reduces the fraction of clasmatodendritic astrocytes in total astrocytes, and accumulation of nuclear p65/RelA-Ser529 phosphorylation (b, arrows). Bar = 15 μm. (c) The quantitative analysis of the fraction of clasmatodendritic astrocytes in the total astrocytes (mean ± SEM). Significant differences from saline-infused animals, *P < 0.05

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