title: Rapid and long-term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsy.
abstract: Alterations of gamma-aminobutyric acid (GABA)B receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABAB receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABAB receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1-CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post-KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABAB receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post-KA. In double-staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1-positive interneurons also increased contralaterally in the hilus. The rapid KA-induced loss of GABAB receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long-term increase in GABAB receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures.
authors: Institute of Pharmacology and Toxicology, University of Zurich, Switzerland.
authors: Andrea
authors: A
authors: Straessle
authors: Fabienne
authors: F
authors: Loup
authors: Dimitrula
authors: D
authors: Arabadzisz
authors: Gordon V
authors: GV
authors: Ohning
authors: Jean-Marc
authors: JM
authors: Fritschy
mesh_terms: D000818:Animals; D002452:Cell Count; D002766:Cholecystokinin / Q000378:metabolism; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013995:Time; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; C485503:GABBR2 protein, human; C485504:Gabbr2 protein, mouse; D009478:Neuropeptide Y; D018080:Receptors, GABA-B; D013004:Somatostatin; D002766:Cholecystokinin; D007608:Kainic Acid