P2X7 receptor differentially modulates astroglial apoptosis and clasmatodendrosis in the rat brain following status epilepticus

Abstract

Recently, it has been reported that astroglial loss/dysfunction plays a role in epileptogenesis. In addition, astroglial loss is accompanied by up-regulation of P2X7 receptor expression in microglia. Therefore, we investigated whether P2X7 receptor is involved in astroglial damages induced by status epilepticus (SE). In the present study, astroglial loss showed the regional-specific manner and the differential responses to P2X7 receptor functions. Both OxATP and brilliant blue G (P2X7 receptor antagonists) infusion prevented apoptotic astroglial loss in the molecular layer of the dentate gyrus and the frontoparietal cortex, while it promoted clasmatodendrosis in the CA1 region as compared to saline treatment. In contrast, BzATP (a P2X7 receptor agonist) treatment exacerbated apoptotic astroglial loss in the molecular layer of the dentate gyrus and the frontoparietal cortex, but alleviated SE-induced astroglial swelling in the CA1 region. Astroglial loss in the piriform cortex was not affected by P2X7 receptor agonist- or antagonist-infusion. These findings suggest that P2X7 receptor function differently modulates SE-induced astroglial loss in distinct brain regions.

Silencing of P2X7R by RNA interference in the hippocampus can attenuate morphological and behavioral impact of pilocarpine-induced epilepsy

“…These data corroborate other studies that also showed reduction in astrocytes loss in the molecular layer of the dentate gyrus and frontoparietal cortex following P2X7R antagonists oxidized ATP (OxATP) and BBG in pilocarpine model [40]. In contrast, some authors showed increased cell death in CA3 layer by using P2X7R antagonists OxATP, A-438079, and A-740003 following pilocarpine [39], and that inhibition of microglial activation by the P2X7R antagonists may not be sufficient to protect neurons of the excitotoxicity caused by SE [43].…”

“…There are many studies aimed at elucidating the role of P2X7R in epilepsy using agonists and antagonists. The activation of P2X7R with Bz-ATP (P2X7R agonist) causes microglial activation, enhances TNF-α immunoreactivity, reduces astrocytes, and intensifies seizures expression [19,[38][39][40]. Conversely, P2X7R blockage promotes anticonvulsant effects and reduces electroencephalographic and behavioral seizures, IL-1β production, microglial activation, recruitment and infiltration of neutrophils into the frontoparietal cortex, and damage resulting from seizure [14,15,33,38,[41][42][43][44].…”

p65/RelA-Ser529 NF-κB Subunit Phosphorylation Induces Autophagic Astroglial Death (Clasmatodendrosis) Following Status Epilepticus

“…Recently, Takenouchi et al (2009) reported that P2X7R activation negatively regulated autophagic flux through the impairment of lysosomal functions. Similarly, we have reported that P2X7R antagonists, such as BBG and OxATP, increased clasmatodendrosis (Kim et al 2010b). With respect to these previous reports, clasmatodendrosis may be one of autophagy-related degeneration of astrocytes following SE.…”

“…We have recently reported that SE results in caspase-3-independent/AIF-dependent apoptosis-like degeneration of astrocytes in the molecular layer of rat dentate gyrus (Kang et al 2006;Kim et al 2008Kim et al , 2010b. SE also induces astroglial death through severe vasogenic edema in the piriform cortex (Kim et al 2010c).…”

“…SE also induces astroglial death through severe vasogenic edema in the piriform cortex (Kim et al 2010c). Although both the dentate gyrus and the piriform cortex show acute astroglial loss in responses to SE, the CA1 region shows clasmatodendrosis as the chronic responses to SE (Kim et al 2010b). Therefore, the vulnerability of astrocytes to SE shows the regional-specific manners like neurons.…”