Role of Endoplasmic Reticulum Stress in the Amygdaloid Kindling Model of Rats

Abstract

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. Seven-week-old rats were divided into three groups: sham (n = 6), partially kindled (n = 8), and over-kindled rats (n = 9). Over kindled rats received over100 stimuli. Partially kindled animals had stimuli halted at stage 2. Protein from ipsilateral hippocampus was electrophoresed on SDS-PAGE, followed by hybridization with primary antibodies, anti-KDEL (-Lys-Asp-Glu-coo-), Bcl-2, BDNF (brain-derived neurotrophic factor), CHOP (C/EBP-homolog protein), C/EBP (CCAAT/enhancer-binding protein), NMDA (N-methyl-D-aspartate; -R1 &2A), GluR1 (glutamate receptor), and β-tubulin. Western blotting revealed that the ER stress marker BiP (immunoglobulin heavy chain-binding protein) was markedly increased in both partially- and over-kindled groups. BiP expression was ninefold greater than control in partially kindling while twofold greater than control in over-kindled animals. Although ER stress response was accelerated, CHOP expression, which upregulates when apoptosis signaling is accelerated by ER stress, was suppressed. Bcl-2, which acts as an anti-apoptotic molecule, was upregulated in the over-kindled group. Remarkable elevation of BiP was found in partially kindled animals, but not in over-kindled. Over-kindled rats had spontaneous generalized seizure, while partially kindled ones had only partial seizures. Elevation of markers of ER stress in partial seizures might reflect transfer of discharge to contralateral limbic structures. We observed indications of functional changes and neurogenesis in limbic structure during kindling. Widespread indications of functional changes in several membrane and secreted proteins, including NMDA-R1 & R2A and BDNF, for mossy fiber re-construction on the CA3 area, which are related to protein synthesis in the ER, may be important in epileptogenesis.

<p>Co-administration of aspirin and adipose-derived stem cell conditioned medium improves the functional recovery of the optic pathway in a lysolecithin-induced demyelination model</p>

“…Several pieces of evidence suggested that aspirin and ADSCs-CM, apart from their immunomodulatory and anti-inflammatory effects, play an important role in promotion of endogenous remyelination. In line with previous reports,33,34,36,39,47 we also showed that local injection of LPC into the rat optic chiasm reduces the conductivity of visual signals and co-administration of ADSCs-CM and aspirin could significantly decrease the latency of VEP waves.…”

“…Lysolecithin (LPC)-induced demyelination model has been introduced as the most common focal demyelination model for evaluation of demyelination and remyelination processes in the CNS 32. Focal injection of LPC into the white matter such as optic chiasm is regarded as a useful approach not only for studying the normal events involved in the remyelination process, but also as a pre-clinical tool for screening of novel remyelination-promoting drugs 33. Visual evoked potential (VEP) recording is widely used in clinical settings to assess the severity of optic neuritis in acute phase of MS disease, and also to monitor the disease course in the follow-up period 34.…”

Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage

“…A variety of pathophysiological and environmental stimuli can disrupt ER homeostasis and proper ER functioning and consequently induce a pathological state known as ER stress (Roussel et al, 2013 ). Several lines of evidence suggest that ER stress is activated in epilepsy disease in both animal and human (Jang et al, 2004 ; Yamamoto et al, 2006 ; Chihara et al, 2011 ; Torres-Peraza et al, 2013 ). Consistent with these studies, here we observed significant ER stress in the hippocampus of PTZ-kindled mice, and this PTZ kindling-induced ER stress is dependent on nNOS activation.…”