title: Expression of GABA receptor subunits in the hippocampus and thalamus after experimental traumatic brain injury.
abstract: Traumatic brain injury is a major cause of death and disability worldwide and often associated with post-traumatic epilepsy. We recently demonstrated that TBI induces acquired GABAA receptors channelopathy that associates with hyperexcitability in granule cell layer (GCL). We now assessed the expression of GABAA and GABAB receptor subunit mRNAs between 6 h and 6 months post-TBI in the hippocampus and thalamus. The expression of major GABAA receptor subunit mRNAs (α1, α2, α5, β2, β3, γ2 and δ) was, often bilaterally, down-regulated in the GCL and in the CA3 pyramidal cells. Instead, expression of α4 (GCL, CA3, CA1), α5 (CA1) and γ2 (GCL, CA3, CA1) mRNA was up-regulated after 10 d and/or 4 months. Many of these changes were reversible. In the thalamus, we found decreases in α1, α4, β2, γ2 and δ mRNAs in the laterodorsal thalamus and in the area combining the posterior thalamic nuclear group, ventroposterolateral and ventroposteromedial complex at 6 h to 4 months post-TBI. Unlike in the hippocampus, thalamic subunit down-regulations were irreversible and limited to the ipsilateral side. However, contralaterally there was up-regulation of the subunits δ and α4 6 h and 4 months after TBI, respectively. PCR array analysis suggested a mild long-lasting GABAA receptor channelopathy in the GCL and thalamus after TBI. Whereas TBI induces transient changes in the expression of GABAA receptor subunits in the hippocampus (presumably representing compensatory mechanisms), alterations of GABAA receptor subunit mRNAs in the thalamus are long-lasting and related to degeneration of receptor-containing neurons in thalamo-cortical relay nuclei.
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria. Electronic address: Meinrad.drexel@i-med.ac.at.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Drexel
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Science, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Puhakka
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Kirchmair
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Heide
authors.initials: H
authors.lastname: Hörtnagl
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Science, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland; Department of Neurology, Kuopio University Hospital, PO Box 1777, FI-70211 Kuopio, Finland.
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkänen
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Sperk
mesh_terms: D000818:Animals; D001345:Autoradiography; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007839:Functional Laterality; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D061346:Laser Capture Microdissection; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D011963:Receptors, GABA-A
keywords: Epilepsy; GABA; Lateral fluid-percussion injury; Neurosteroid