Endoplasmic reticulum (ER) stress protein responses in relation to spatio-temporal dynamics of astroglial responses to status epilepticus in rats

• SE results in neuronal- and astroglial-ER stress in the rat hippocampus.
• Up-regulated PDI expression is associated with astroglial apoptosis.
• Increased CNX expression is detected in clasmatodendritic astrocytes.
• SE-induced ER stress is relevant to regional-specific astroglial loss.

In the present study, we investigated whether endoplasmic reticulum (ER) stress is associated with neuronal- and astroglial-death in the hippocampus using LiCl-pilocarpine-induced status epilepticus (SE) rat model. Glucose-related protein (GRP) 78 and protein disulfide isomerase (PDI) expressions were transiently increased in CA1 neurons and dentate granule cells, and subsequently decreased in these cells following SE. GRP94 and calnexin (CNX) expression was gradually reduced in CA1 neurons, not in dentate granule cells. Phospho-protein kinase RNA (PKR)-like ER kinase (pPERK), phospho-eukaryotic initiation factor 2α (peIF2A) and CCAAT/enhancer-binding protein homologous protein (CHOP) immunoreactivities were observed in 17%, 12% and 7% of degenerating CA1 neurons, respectively. GRP 78 and PDI expressions were also up-regulated in reactive astrocytes within the CA1–3 regions. In the molecular layer of the dentate gyrus, PDI-positive astrocytes showed TUNEL signal, nuclear apoptosis inducing factor translocation and pPERK/peIF2A/CHOP immunoreactivities. Four weeks after SE, clasmatodendritic astrocytes showed pPERK peIF2A and CNX immunoreactivities without CHOP expression. These findings indicate that SE-induced ER stress may be associated with astroglial apoptosis and autophagic astroglial death in the regional-specific pattern.