[en] Differential mRNA display was carried out to find genes that are differentially regulated in the brain of a rat strain with absence epilepsy, the genetic absence epilepsy rats from Strasbourg (GAERS). Among the 32 differentially displayed cDNA fragments actually cloned and sequenced, one shows 100% identity with the rat heavy chain ferritin (H-ferritin) mRNA. Northern blot analysis confirmed the up-regulation of the H-ferritin mRNA. Using dot blotting, a 40% increase in expression was reported in the subcortical forebrain of the adult GAERS, while cortex, brain stem, and cerebellum appeared unmodified. This change was not observed in the brain of 25-day-old rats, an age at which the epileptic phenotype is not present. By in situ hybridization, the enhanced expression was localized in the hippocampus. The increase in mRNA encoding H-ferritin was not immunodetected at the protein level by Western blotting. These results are not apparently related to the neural substrate of SWD or to the distribution of local increase in glucose metabolism previously described in the GAERS. It is hypothesized that the up-regulation of the H-ferritin mRNA is part of a mechanism protecting the hippocampus, a seizure-prone area, against a possible overactivation during absence seizures.
Disciplines :
Neurosciences & behavior
Author, co-author :
Lakaye, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
de Borman, B.
Minet, Arlette ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Arckens, L.
Vergnes, M.
Marescaux, C.
Grisar, Thierry ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Language :
English
Title :
Increased Expression of mRNA Encoding Ferritin Heavy Chain in Brain Structures of a Rat Model of Absence Epilepsy
Andrews S. C., Arosio P., Bottke W., Briat J. F., von Darl M., Harrison P. M., Lauihère J. P., Levi S., Lobreaux S., Yewdall S. J. Structure, function and evolution of ferritins. J. Inorg. Biochem. 47:1992;161-174.
Arckens L., Zhang F., Vanduffel W., Mailleux P., Vanderhaeghen J. J., Orban G. A., Vandesande F. Localization of the two protein kinase Cβ-mRNA subtypes in cat visual system. J. Chem. Neuroanat. 8:1995;117-124.
Avoli M., Gloor P. Role of the thalamus in generalized penicillin epilepsy: Observations on decorticated cats. Exp. Neurol. 77:1982;386-402.
Bevilacqua M. A., Faniello M. C., D'Agostino P., Quaresima B., Tiano M. T., Pignata S., Russo T., Cimino F., Costanzo F. Transcriptional activation of the H-ferritin gene in differentiated Caco-2 cells parallels a change in the activity of the nuclear factor Bbf. Biochem. J. 311:1995;769-773.
Cairo G., Rappocciolo E., Tacchini L., Schiaffonati L. Expression of the genes for the ferritin H and L subunits in rat liver and heart. Biochem. J. 275:1991;813-816.
Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:1987;156-159.
Connor J. R., Menzies S. L., St S. M., Mufson E. J. Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains. J. Neurosci. Res. 27:1990;595-611.
Crunelli V., Leresche N. A role for GABAB receptors in excitation and inhibition of thalamocortical cells. Trends Neurosci. 14:1991;16-21.
Dwyer K. J., Boado R. J., Pardridge W. M. Cis-element/cytoplasmic protein interaction within the 3′-untranslated region of the GLUT1 glucose transporter mRNA. J. Neurochem. 66:1996;449-458.
Gloor P., Fariello G. Generalized epilepsy: Some of its cellular mechanisms differ from those of focal epilepsy. Trends. Neurosci. 11:1988;63-68.
Guyon A., Vergnes M., Leresche N. Thalamic low treshold calcium current in a genetic model of absence epilepsy. NeuroReport. 4:1993;1231-1234.
Hentze M. W., Caughman S. W., Rouault T. A., Barriocanal J. G., Dancis A., Harford J. B., Klausner R. D. Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science. 238:1987;1570-1573.
Iwasa Y., Aida K., Yokomori N., Inoue M., Onaga T. Transcriptional regulation of ferritin heavy chain messenger RNA expression by thyroid hormone. Biochem. Biophys. Res. Commun. 167:1990;1279-1285.
Kitahara T., Kiryu S., Takeda N., Kubo T., Kiyama H. Up-regulation of ferritin heavy chain mRNA expression in the rat skeletal muscle after denervation: Detection by means of differential display. Neurosci. Res. 23:1995;353-360.
Knight A. R., Bowery N. G. GABA receptors in rats with spontaneous generalized nonconvulsive epilepsy. J. Neural Transm. Suppl. 35:1992;189-196.
Lason W., Przewlocka B., Van Luijtelaar G., Coenen A. Proenkephalin and prodynorphin mRNA level in brain of rats with absence epilepsy. Neuropeptides. 27:1994;343-347.
Liang P., Pardee A. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science. 257:1992;967-971.
Liau G., Chan L. M., Feng P. Increased ferritin gene expression is both promoted by cAMP and a marker of growth arrest in rabbit vascular smooth muscle cells. J. Biol. Chem. 266:1991;18819-18826.
Marescaux C., Vergnes M., Depaulis A. Genetic absence epilepsy in rats from Strasbourg: A review. J. Neural. Transm. Suppl. 35:1992;179-188.
Mathivet P., Bernasconi R., Reymann N., Marescaux C., Vergnes M., Bittiger H. Different binding characteristics of cortical GABAB receptors in GAERS compared to non epileptic control rats using agonist and antagonist radioligands. Pharmacol. Rev. Commun. 8:1996;203-207.
Munro H. The ferritin genes: Their response to iron status. Nutr. Rev. 51:1993;65-73.
Nehlig A., Vergnes M., Marescaux C., Boyet S., Lannes B. Local cerebral glucose utilization in rats with petit mal-like seizures. Ann. Neurol. 29:1991;72-77.
Nehlig A., Vergnes M., Boyet S., Marescaux C. Metabolic activity is increased in discrete brain regions before the occurence of spike-and-wave discharges in weanling rats with genetic absence epilepsy. Dev. Brain Res. 108:1998;69-75.
Qi Y., Dawson G. Hypoxia specifically and reversibly induces the synthesis of ferritin in oligodendrocytes and human oligodendrogliomas. J. Neurochem. 63:1994;1485-1490.
Qiao X., Noebels J. L. Developmental analysis of hippocampal mossy fiber outgrowth in a mutant mouse with inherited spike-wave seizures. J. Neurosci. 13:1993;4622-4635.
Roskams A. J. I., Connor J. R. Iron, transferrin, and ferritin in the rat brain during development and aging. J. Neurochem. 63:1994;709-716.
Sanyal B., Polak P. E., Szuchet S. Differential expression of the heavy-chain ferritin gene in non adhered and adhered oligodendrocytes. J. Neurosci. Res. 46:1996;187-197.
Snead O. C., Depaulis A., Banerjee P. K., Hechler V., Vergnes M. The GABAA receptor complex in experimental absence seizures in rat: An autoradiographic study. Neurosci. Lett. 140:1992;9-12.
Stanfield B. B. Excessive intra and supragranular mossy fibers in the dentate gyrus of tottering (tg/tg) mice. Brain Res. 480:1989;294-299.
Torti S. V., Kwak E. L., Miller S. C., Miller L. L., Ringold G. M., Myambo K. B., Young A. P., Torti F. M. The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene. J. Biol. Chem. 263:1988;12638-12644.
Tsakiridou E., Bertollini L., de Curtis M., Avanzini G., Pape H. C. Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. J. Neurosci. 15:1995;3110-3117.
Vergnes M., Marescaux C., Micheletti G., Warter M. Spontaneous SWD in thalamus and cortex in a rat model of genetic petit mal epilepsy. Exp. Neurol. 96:1987;127-136.
Wei Y., Miller S. C., Tsuji Y., Torti S. V., Torti F. M. Interleukin 1 induces ferritin heavy chain in human muscle cells. Biochem. Biophys. Res. Commun. 169:1990;289-296.
Wrigglesworth J. M., Baum H. Iron dependent enzymes in the brain. Youdim M. B. H. Topics in Neurochemistry and Neuropharmacology, Vol. 2, Brain Iron Neurochemical and Behavioral Aspects. 1988;25-66 Taylor and Francis, London.
Yokomori N., Iwasa Y., Aida K., Inoue M., Tawata M., Onaya T. Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. Endocrinology. 128:1991;1474-1480.