Abstracts

Rationale: Endoplasmic Reticulum (ER) is an organelle responsible for correct folding and sorting of proteins contributing to neurogenesis and neuronal cell death. We used rapid kindling to analyze specific ER stress marker expression underlying focal epileptogenesis and to correlate ER stress and neuronal apoptotic changes. Methods: Seven-weeks-old rats in 3 groups: sham (n=6), partial kindled rats (n=8), and over-kindled rats (n=9). Over kindled rats received over100 stimuli. Partial kindled animals had stimuli halted at Stage 2. Protein from ipsilateral hippocampus was electrophoresed on SDS-PAGE, followed by hybridized with primary antibodies, anti-KDEL, Bcl-2, BDNF, CHOP, NMDA-R1 &2A, GluR1, and ?-tubulin. Results: Western blotting revealed that the ER stress marker BiP was markedly increased in both partial- and over-kindled groups. BiP expression was 9-fold greater than control in partial-kindling while 2-fold greater than control in over-kindled animals. Although ER stress response was accelerated, CHOP expression, which up-regulates when apoptosis signaling is accelerated by ER stress, was suppressed. Bcl-2, which acts as an anti-apoptotic molecule, was up-regulated in the over-kindled group. Conclusions: Remarkable elevation of BiP was found in partial kindled animals, but not in over-kindled. Elevation of markers of ER stress in partial seizures might reflect transfer of discharge to contralateral limbic structures. We observed functional changes and neurogenesis in limbic structure during kindling. Wide-spread functional changes in several membrane and secreted proteins, including NMDA-R1&R2A and BDNF, for mossy fiber re-construction on CA3 area, that are related to protein synthesis in ER, may be of importance in epileptogenesis.