Regional Changes in Gene Expression after Limbic Kindling

Abstract

Repeated electrical stimulation results in development of seizures and a permanent increase in seizure susceptibility (kindling). The permanence of kindling suggests that chronic changes in gene expression are involved. Kindling at different sites produces specific effects on interictal behaviors such as spatial cognition and anxiety, suggesting that causal changes in gene expression might be restricted to the stimulated site. We employed focused microarray analysis to characterize changes in gene expression associated with amygdaloid and hippocampal kindling. Male Long-Evans rats received 1 s trains of electrical stimulation to either the amygdala or hippocampus once daily until five generalized seizures had been kindled. Yoked control rats carried electrodes but were not stimulated. Rats were euthanized 14 days after the last seizures, both amygdala and hippocampus dissected, and transcriptome profiles compared. Of the 1,200 rat brain-associated genes evaluated, 39 genes exhibited statistically significant expression differences between the kindled and non-kindled amygdala and 106 genes exhibited statistically significant differences between the kindled and non-kindled hippocampus. In the amygdala, subsequent ontological analyses using the GOMiner algorithm demonstrated significant enrichment in categories related to cytoskeletal reorganization and cation transport, as well as in gene families related to synaptic transmission and neurogenesis. In the hippocampus, significant enrichment in gene expression within categories related to cytoskeletal reorganization and cation transport was similarly observed. Furthermore, unique to the hippocampus, enrichment in transcription factor activity and GTPase-mediated signal transduction was identified. Overall, these data identify specific and unique neurochemical pathways chronically altered following kindling in the two sites, and provide a platform for defining the molecular basis for the differential behaviors observed in the interictal period.

Deep brain stimulation effects on learning, memory and glutamate and GABAA receptor subunit gene expression in kindled rats

“…These findings were in line with previous studies that memory impairments could be observed less than 3-4 weeks after the final kindling stimulation in animals with generalized seizures (Lopes da Silva et al, 1986;Feasey-Truger et al, 1993;Gilbert et al, 2000). Similar to our results, no changes in the gene expression level of GABA A (Kamphuis et al, 1995b;Nishimura et al, 2005) and NMDA (Kamphuis et al, 1995a;Corcoran et al, 2011) receptor subunits have been reported at 2-4 weeks following the last kindling stimulation.…”

Astroglial Ca2+-Dependent Hyperexcitability Requires P2Y1 Purinergic Receptors and Pannexin-1 Channel Activation in a Chronic Model of Epilepsy

“…Male Sprague-Dawley rats (at 35 postnatal days, p35) were anesthetized and subjected to stereotactic surgery for electrode implantation (Greenwood et al, 1991 ; Corcoran et al, 2011 ). Five electrodes were implanted: one in the right basolateral amygdala complex for stimulation and recording; and two bilaterally implanted pairs for recording in the primary motor (Br.…”

A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

“…The surgical procedures for electrode implantation were carried out as described (Greenwood et al, 1991; Corcoran et al, 2011), with minor modifications. The skull was leveled and a teflon insulated bipolar stimulating and recording electrode of twisted stainless steel (0.2 mm of outer diameter, Plastics One Inc.) implanted in the right BLA to deliver kindling stimulation and record the ADs after the stimulus ended.…”