Regional Changes in Gene Expression after Limbic Kindling
- 225 Downloads
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.
KeywordsKindling Microarray Hippocampus Amygdala NMDA receptor
This work is supported in part by grants from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council (to MEC) and The Falk Foundation, Chicago, IL, (to JRM). We thank Joanne Sitarski, Ken Wolfe, Nigel Otto, and Mary Schmidt for expert technical assistance.
- Burgdorf J, Zhang XL, Weiss C, Matthews E, Disterhoft JF, Stanton PK, Moskal JR (2009) The N-methyl-d-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats. Neurobiol AgingGoogle Scholar
- Corcoran ME, Moshé SL (eds) (1998) Kindling five. Plenum, New YorkGoogle Scholar
- Corcoran ME, Moshé SL (eds) (2005) Kindling six. Springer, New YorkGoogle Scholar
- Endele S, Rosenberger G, Geider K, Popp B, Tamer C, Stefanova I, Milh M, Kortum F, Fritsch A, Pientka FK, Hellenbroich Y, Kalscheuer VM, Kohlhase J, Moog U, Rappold G, Rauch A, Ropers HH, von Spiczak S, Tonnies H, Villeneuve N, Villard L, Zabel B, Zenker M, Laube B, Reis A, Wieczorek D, Van Maldergem L, Kutsche K (2010) Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat Genet 42:1021–1026PubMedCrossRefGoogle Scholar
- Goddard GV, Douglas RM (1976) Does the engram of kindling model the engram of normal long term memory? In: Wada JA (ed) Kindling. Raven, New York, p 18Google Scholar
- Racine RJ, Burnham WM, Gilbert M, Kairiss EW (1986) Kindling mechanisms: I. Electrophysiological studies. In: Wada JA (ed) Kindling three. Raven, New York, pp 263–279Google Scholar
- Schinnick-Gallagher P, Bradley Keele N (1998) Long-lasting changes in the pharmacology and electrophysiology of amino acid receptors in amygdala kindled neurons. In: Corcoran ME, Moshé SL (eds) Kindling five. Plenum, New York, pp 75–87Google Scholar