QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) An erratum has been published Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (68) Citing Articles via Google Scholar Google Scholar Articles by Poulter, M. O. Articles by McIntyre, D. C. Search for Related Content PubMed PubMed Citation Articles by Poulter, M. O. Articles by McIntyre, D. C.

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 1, 1999, 19(11):4654-4661

Differential Expression of ₁, ₂, ₃, and ₅ GABA_A Receptor Subunits in Seizure-Prone and Seizure-Resistant Rat Models of Temporal Lobe Epilepsy

Michael O. Poulter¹, Leslie A. Brown¹, Stephen Tynan¹, Gordon Willick², Ross William², and Dan C. McIntyre³

¹ Laboratory of Molecular Neuropharmacology and ² Vaccine Design Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada, K1A 0R6, and ³ Institute for Neuroscience, Carleton University, Ottawa, Ontario, Canada, K1S 5B6

Temporal lobe epilepsy remains one of the most widespread seizure disorders in man, the etiology of which is controversial. Using new rat models of temporal lobe epilepsy that are either prone or resistant to develop complex partial seizures, we provide evidence that this seizure susceptibility may arise from arrested development of the GABA_A receptor system. In seizure-prone (Fast kindling) and seizure-resistant (Slow kindling) rat models, both the mRNA and protein levels of the major  subunit expressed in adult brain (₁), as well as those highly expressed during development (₂, ₃, and ₅), were differentially expressed in both models compared with normal controls. We found that ₁ subunit mRNA expression in the Fast kindling strain was approximately half the abundance of control rats, whereas in the Slow kindling strain, it was ~70% greater than that of controls. However, Fast rats overexpressed the ₂, ₃, and ₅ ("embryonic") subunits, having a density 50-70% greater than controls depending on brain area, whereas the converse was true of Slow rats. Using subunit-specific antibodies to ₁ and ₅ subunits, quantitative immunoblots and immunocytochemistry revealed a concordance with the mRNA levels. ₁ protein expression was ~50% less than controls in the Fast strain, whereas it was 200% greater in the Slow strain. In contrast, ₅ subunit protein expression was greater in the Fast strain than either the control or Slow strain. These data suggest that a major predispositional factor in the development of temporal lobe epilepsy could be a failure to complete the normal switch from the GABA_A receptor  subunits highly expressed during development (₂, ₃, and ₅) to those highly expressed in adulthood (₁).

Key words: GABA_A; epilepsy; receptors; kindling; ion channels; seizure; temporal lobe epilepsy

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/19114654-08$05.00/0

This article has been cited by other articles:

				D. L. Jones and S. C. Baraban Inhibitory Inputs to Hippocampal Interneurons Are Reorganized in Lis1 Mutant Mice J Neurophysiol, August 1, 2009; 102(2): 648 - 658. [Abstract] [Full Text] [PDF]

				J. Epsztein, Y. Ben-Ari, A. Represa, and V. Crepel Late-Onset Epileptogenesis and Seizure Genesis: Lessons From Models of Cerebral Ischemia Neuroscientist, February 1, 2008; 14(1): 78 - 90. [Abstract] [PDF]

				A. K. Sharma, R. Y. Reams, W. H. Jordan, M. A. Miller, H. L. Thacker, and P. W. Snyder Mesial Temporal Lobe Epilepsy: Pathogenesis, Induced Rodent Models and Lesions Toxicol Pathol, December 1, 2007; 35(7): 984 - 999. [Abstract] [Full Text] [PDF]

				K. Schwabe, C. Gavrilovici, D. C. McIntyre, and M. O. Poulter Neurosteroids Exhibit Differential Effects on mIPSCs Recorded From Normal and Seizure Prone Rats J Neurophysiol, September 1, 2005; 94(3): 2171 - 2181. [Abstract] [Full Text] [PDF]

				T. A. Simeone, S. D. Donevan, and J. M. Rho Molecular Biology and Ontogeny of {gamma}-Aminobutyric Acid (GABA) Receptors in the Mammalian Central Nervous System J Child Neurol, January 1, 2003; 18(1): 39 - 48. [Abstract] [PDF]

				D. C. McIntyre, B. Hutcheon, K. Schwabe, and M. O. Poulter Divergent GABAA Receptor-Mediated Synaptic Transmission in Genetically Seizure-Prone and Seizure-Resistant Rats J. Neurosci., November 15, 2002; 22(22): 9922 - 9931. [Abstract] [Full Text] [PDF]

				J. E. Kralic, E. R. Korpi, T. K. O'Buckley, G. E. Homanics, and A. L. Morrow Molecular and Pharmacological Characterization of GABAA Receptor alpha 1 Subunit Knockout Mice J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 1037 - 1045. [Abstract] [Full Text] [PDF]

				H. Anisman and D. C. McIntyre Conceptual, Spatial, and Cue Learning in the Morris Water Maze in Fast or Slow Kindling Rats: Attention Deficit Comorbidity J. Neurosci., September 1, 2002; 22(17): 7809 - 7817. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help