Hyperthermia-Induced Seizures Modify the GABAA and Benzodiazepine Receptor Binding in Immature Rat Brain
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Effects of hyperthermia-induced seizures (HS) on GABAA and benzodiazepine (BDZ) receptor binding in immature rat brain were evaluated using in vitro autoradiography. HS were induced in 10-days-old rats by a regulated stream of moderately heated air directed 50 cm above the animals. Rats were killed 30 min, 24 h or 20 days after HS and their brains were used for in vitro autoradiography experiments to determine GABAA and BDZ receptor binding. GABAA binding was significantly enhanced in all brain areas evaluated 30 min after HS, an effect that endures 24 h and 20 days after seizures. Concerning BDZ receptor binding, a significant increase was detected in entorhinal and perirhinal cortices and decreased in basolateral amygdala 30 min following HS. One day after HS, animals demonstrated enhanced BDZ binding in the cingulate, frontal, posterior parietal, entorhinal, temporal and perirhinal cortices; striatum, accumbens, substantia nigra pars compacta and amygdala nuclei. Twenty days after HS enhanced BDZ binding was restricted in the cingulated, frontal, anterior and posterior parietal cortices, as well as in substantia nigra pars reticulata, whereas decreased values were found in accumbens nucleus and substantia nigra pars compacta. Our data indicate differential effects of HS in GABAA and BDZ binding in immature brain. HS-induced GABAA and BDZ changes are different from those previously described in experimental models of temporal lobe epilepsy in adult animals.
KEY WORDS:GABAA receptors benzodiazepine receptors immature brain febrile seizures hyperthermia-induced seizures
We thank Leticia Neri, Magdalena Briones and Héctor Vázquez for their excellent technical assistance. Isabel Pérez Montfort corrected the English version of the manuscript. This study was supported by a grant from Coordination of Research in Health from Mexican Institute of Social Security (grant no. FP-2002/103) and CONACyT (grant 45943-M).
- Bowser, D. N., Wagner, D. A., Czajkowski, C., Cromer, B. A., Parker, M. W., Wallace, R. H., Harkin, L. A., Mulley, J. C., Marini, C., Berkovic, S. F., Williams, D. A., and Jones, M. V. (2002). Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation (γ2(R43Q)) found in human epilepsy. PNAS 99:15170–15175.PubMedCrossRefGoogle Scholar
- Brooks-Kayal, A. R., Shumate, M. D., Jin, H., Rikhter, T. Y., Kelly, M. E., and Coulter, D. A. (2001). γ-Aminobutyric acidA receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development. J. Neurochem. 77:1266–1278.PubMedCrossRefGoogle Scholar
- Cendes, F., Andermann, F., Dubeau, F., Gloor, P., Evans, A., Jones-Gotman, M., Olivier, A., Andermann, E., Robitaille, Y., Lopes-Cendes, I., Peters, T., and Melanson, D. (1993). Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures and temporal lobe epilepsy: An MRI volumetric study. Neurology 43:1083–1087.PubMedGoogle Scholar
- Consensus Development Panel (1980). Febrile seizures: Long-term management of children with fever-associated seizures. Pediatrics 66:1009–1012.Google Scholar
- Harkin, L. A., Bowser, D. N., Dibbens, L. M., Singh, R., Phillips, F., Wallace, R. H., Richards, M. C., Williams, D. A., Mulley, J. C., Berkovic, S. F., Scheffer, I. E., and Petrou, S. (2002). Truncation of the GABAA-receptor γ2 subunit in a family with generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 70:530–536.PubMedCrossRefGoogle Scholar
- Hayashi, T. (1952). The efferent pathway of epileptic seizures for the face following cortical simulation differs from that for the limbs. Jpn. J. Physiol. 3:306–321.Google Scholar
- Jinnai, D., Yoshida, T., Sonji, T., and Kosaka, F. (1954). Experimental studies on the march of spasm during an epileptic convulsion. Acta Medica Okayama. 8:26–29.Google Scholar
- Moshé, S. L., and Sperber, E. F. (1990). Substantia nigra-mediated control of generalized seizures. In: Gloor, G., and Naquet, R., (eds.), Generalized Epilepsy: Cellular, Molecular, and Pharmacological Approaches. Birkhauser Inc., Boston, pp. 355–367.Google Scholar
- Paxinos, G., and Watson, C. (1998). The rat brain in stereotaxic coordinates. In Paxino (ed.), Academic Press, London UK.Google Scholar
- Wallace, R. H., Marini, C., Petrou, S., Harkin, L. A., Bowser, D. N., Panchal, R. G., Williams, D. A., Sutherland, G. R., Mulley, J. C., Scheffer, I. E., and Berkovic, S. F. (2001). Mutant GABAA receptor γ2-subunit in childhood absence epilepsy and febrile seizures. Nat. Genet. 28:49–52.PubMedCrossRefGoogle Scholar