Kainic acid-induced status epilepticus alters GABA receptor subunit mRNA and protein expression in the developing rat hippocampus.
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 GABAAalpha1-alpha5, beta1-beta3, gamma1 and gamma2 subunit mRNA expression in the hippocampus of 9-day-old rats during 1 week after the treatment. Immunocytochemistry was applied to detect the alpha1, alpha2 and beta3 subunit proteins in the control and treated rats. In the saline-injected control rats, the alpha1 and alpha4 subunit mRNA expression significantly increased between the postnatal days 9-16, whereas those of alpha2, beta3 and gamma2 subunits decreased. The normal developmental changes in the expression of alpha1, alpha2, beta3 and gamma2 subunit mRNAs were altered after the treatment. The immunostainings with antibodies to alpha1, alpha2 and beta3 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.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
H B
HB
Laurén
F R
FR
Lopez-Picon
E R
ER
Korpi
I E
IE
Holopainen
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D005452:Fluoresceins; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007608:Kainic Acid; D009930:Organic Chemicals; D010640:Phenothiazines; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013194:Staining and Labeling; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
D005452:Fluoresceins; D009930:Organic Chemicals; D010640:Phenothiazines; D020033:Protein Isoforms; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C435731:fluoro jade; D007608:Kainic Acid; C009469:thionine