[en] Purpose: We present results obtained by computer modeling of the thalamic network and differential gene expression analysis in a rat strain with absence epilepsy, the genetic absence epilepsy rat from Strasbourg (GAERS). Methods: (a) Computer modeling used equations from the Hodgking-Huxley model with a circuit of 13 reticular thalamic (nRt) and 39 thalamocortical (TC) neurons; (b) gene-expression analysis using differential mRNA display (DD), in situ hybridization, Northern blotting, and competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Results: (a) Computer modeling showed an increased network synchrony in the thalamic circuit as the value of conductance of low-voltage activated calcium channel (LVACC) is increased. (b) Using differential mRNA display, a 40% upregulation of the H-ferritin mRNA in the hippocampus was demonstrated. Looking for some candidate genes of the VACC family, no difference was found in the alpha1G mRNA expression between GAERS and control animals, whereas a decreased expression of the alpha1E subunit was observed in the cerebellum and the brainstem of the GAERS. This phenomenon was not observed in young animals when the epileptic phenotype is not expressed. Conclusions: The use of computer modeling appeared to be an efficient way to evaluate the impacts of electrophysiologic findings in vivo from single cells on an entire circuit. No clear single gene defect was revealed so far in GAERS. More information could arise from linkage analysis. However, some brain structures like hippocampus or cerebellum classically not known to be involved in the production of absence spike-and-wave discharges could in fact participate in the development of this phenotype.
Disciplines :
Neurology
Author, co-author :
Lakaye, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Thomas, E.
Minet, Arlette ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Grisar, Thierry ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Language :
English
Title :
The genetic absence epilepsy rat from Strasbourg (GAERS), a rat model of absence epilepsy: Computer modeling and differential gene expression
Publication date :
2002
Journal title :
Epilepsia
ISSN :
0013-9580
eISSN :
1528-1167
Publisher :
Blackwell Publishing Inc, Malden, United States - Massachusetts
Marescaux, C., Vergnes, M., Depaulis, A., Genetic absence epilepsy in rats from Strasbourg (1992) J Neural Transm, 35 (SUPPL.), pp. 37-69
Avoli, M., Gloor, P., Role of the thalamus in generalized penicillin epilepsy: Observations on decorticated cats (1982) Exp Neurol, 77, pp. 386-402
Gloor, P., Fariello, G., Generalized epilepsy: Some of its cellular mechanisms differ from those of focal epilepsy (1988) Trends Neurosci, 11, pp. 63-68
Crunelli, V., Leresche, N., A role for GABAB receptors in excitation and inhibition of thalamocortical cells (1991) Trends Neurosci, 14, pp. 16-21
Charpier, S., Leresche, N., Deniau, J.M., On the putative contribution of GABA(B) receptors to the electrical events occurring during spontaneous spike and wave discharges (1999) Neuropharmacology, 38, pp. 1699-1706
Knight, A.R., Bowery, N.G., GABA receptors in rats with spontaneous generalized nonconvulsive epilepsy (1992) J Neural Transm, 35 (SUPPL.), pp. 189-196
Mathivet, P., Bernasconi, R., Reymann, N., Different binding characteristics of cortical GABAB receptors in GAERS compared to nonepileptic control rats using agonist and antagonist radioligands (1996) Pharmacol Rev Commun, 8, pp. 203-207
Tsakiridou, E., Bertollini, L., De Curtis, M., Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy (1995) J Neurosci, 15, pp. 3110-3117
Thomas, E., Grisar, T., Increased synchrony with increase of low-threshold calcium conductance in a model thalamic network: A phase-shift mechanism (2000) Neural Comput, 12, pp. 1553-1571
De Borman, B., Lakaye, B., Minet, A., Expression of mRNA encoding α1E and α1G subunit in the brain of a rat model of absence epilepsy (1999) Neuroreport, 10, pp. 569-574
Lakaye, B., De Borman, B., Minet, A., Increased expression of mRNA endoding ferrtin heavy chain in brain structures of a rat model of absence epilepsy (2000) Exp Neurol, 162, pp. 112-120
Chomczynski, P., Sacchi, N., Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction (1987) Anal Biochem, 162, pp. 156-159
Liang, P., Pardee, A., Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction (1992) Science, 257, pp. 967-971
Holter, J.L., Crunelli, V., Leresche, N., Gene expression profile in the GAERS model of absence epilepsy (2000) Soc Neurosci Abstr, 26, p. 1178
Nehlig, A., Vergnes, M., Marescaux, C., Cerebral energy metabolism in rats with genetic absence epilepsy is not correlated with the pharmacological increase or suppression of spike-wave discharge (1993) Brain Res, 618, pp. 1-8
Nehlig, A., Vergnes, M., Boyet, S., Metabolic activity is increased in discrete brain regions before the occurrence of spike-and-wave discharges in weanling rats with genetic absence epilepsy (1998) Dev Brain Res, 108, pp. 69-75
Qiao, X., Noebels, J.L., Developmental analysis of hippocampal mossy fiber outgrowth in a mutant mouse with inherited spike-wave seizures (1993) J Neurosci, 13, pp. 4622-4635
Stanfield, B.B., Excessive intra and supragranular mossy fibers in the dentate gyrus of tottering (tg/tg) mice (1989) Brain Res, 480, pp. 294-299
Snead O.C. III, Depaulis, A., Banerjee, P.K., The GABAA receptor complex in experimental absence seizures in rat: An autoradiographic study (1992) Neurosci Lett, 140, pp. 9-12
Lason, W., Przewlocka, B., Van Luijtelaar, G., Proenkephalin and prodynorphin mRNA level in brain of rats with absence epilepsy (1994) Neuropeptides, 27, pp. 343-347
Talley, E.M., Solorzano, G., Depaulis, A., Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat (2000) Mol Brain Res, 75, pp. 159-165
Barun, S., Lin, F.H., Hosford, D.A., Expression of voltage-dependent calcium channel (VDCC) subunits α1A, β1, β2 and β3 in lethargic (LH/LH) mouse model of absence seizures (1998) Soc Neurosc Abstr, 24, p. 1824
Wray, D.V., Hablitz, J.J., Neuronal firing patterns during generalized penicillin epilepsy in the awake cat (1977) Brain Res Bull, 2, pp. 317-321
Kandel, A., Buzsaki, G., Cerebellar neuronal activity correlates with spike and wave EEG patterns in rat (1993) Epilepsy Res, 16, pp. 1-9
Danober, L., Deransart, C., Depaulis, A., Pathophysiological mechanisms of genetic absence epilepsy in the rat (1998) Prog Neurobiol, 55, pp. 27-57
Mc Enery, M.W., Copeland, T.D., Vance, C.L., Altered expression and assembly of N-type calcium channel alpha 1B and beta subunits in epileptic lethargic (1h/1h) mouse (1998) J Biol Chem, 273, pp. 21435-21438
Walker, D., De Waard, M., Subunit interaction sites in voltage-dependent Ca++ channels: Role in channel function (1998) Trends Neurosci, 21, pp. 148-154