Kainic acid-induced status epilepticus alters GABAA receptor subunit mRNA and protein expression in the developing rat hippocampus

Authors


Address correspondence and reprint requests to Holopainen I. E., MD, PhD, Department of Pharmacology and Clinical Pharmacology, PharmaCity, University of Turku, Itäinen Pitkäkatu 4, FI-20520 Turku, Finland. E-mail: irma.holopainen@utu.fi

Abstract

Kainic acid-induced status epilepticus leads to structural and functional changes in inhibitory GABAA receptors in the adult rat hippocampus, but whether similar changes occur in the developing rat is not known. We have used in situ hybridization to study status epilepticus-induced changes in the GABAAα1–α5, β1–β3, γ1 and γ2 subunit mRNA expression in the hippocampus of 9-day-old rats during 1 week after the treatment. Immunocytochemistry was applied to detect the α1, α2 and β3 subunit proteins in the control and treated rats. In the saline-injected control rats, the α1 and α4 subunit mRNA expression significantly increased between the postnatal days 9–16, whereas those of α2, β3 and γ2 subunits decreased. The normal developmental changes in the expression of α1, α2, β3 and γ2 subunit mRNAs were altered after the treatment. The immunostainings with antibodies to α1, α2 and β3 subunits confirmed the in situ hybridization findings. No neuronal death was detected in any hippocampal subregion in the treated rats. Our results show that status epilepticus disturbs the normal developmental expression pattern of GABAA receptor subunit in the rat hippocampus during the sensitive postnatal period of brain development. These perturbations could result in altered functional and pharmacological properties of GABAA receptors.

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