title: Acute changes in the neuronal expression of GABA and glutamate decarboxylase isoforms in the rat piriform cortex following status epilepticus.
abstract: The piriform cortex (PC) is the largest region of the mammalian olfactory cortex with strong connections to other limbic structures, including the amygdala, hippocampus, and entorhinal cortex. In addition to its functional importance in the classification of olfactory stimuli, the PC has been implicated in the study of memory processing, spread of excitatory information, and the facilitation and propagation of seizures within the limbic system. Previous data from the kindling model of epilepsy indicated that alterations in GABAergic inhibition in the transition zone between the anterior and posterior PC, termed here central PC, are particularly involved in the processes underlying seizure propagation. In the present study we studied alterations in GABAergic neurons in different parts of the PC following seizures induced by kainate or pilocarpine in rats. GABA neurons were labeled either immunohistochemically for GABA or its synthesizing enzyme glutamate decarboxylase (GAD) or by in situ hybridization using antisense probes for GAD65 and GAD67 mRNAs. For comparison with the PC, labeled neurons were examined in the basolateral amygdala, substantia nigra pars reticulata, and the hippocampal formation. In the PC of controls, immunohistochemical labeling for GABA and GAD yielded consistently higher neuronal densities in most cell layers than labeling for GAD65 or GAD67 mRNAs, indicating a low basal activity of these neurons. Eight hours following kainate- or pilocarpine-induced seizures, severe neuronal damage was observed in the PC. Counting of GABA neurons in the PC demonstrated significant decreases in densities of neurons labeled for GABA or GAD proteins. However, a significantly increased density of neurons labeled for GAD65 and GAD67 mRNAs was determined in layer II of the central PC, indicating that a subpopulation of remaining neurons up-regulated the mRNAs for the GAD isoenzymes. One likely explanation for this finding is that remaining GABA neurons in layer II of the central PC maintain high levels of activity to control the increased excitability of the region. In line with previous studies, an up-regulation of GAD67 mRNA, but not GAD65 mRNA, was observed in dentate granule cells following seizures, whereas no indication of such up-regulation was determined for the other brain regions examined. The data substantiate the particular susceptibility of the central PC to seizure-induced plasticity and indicate that this brain region provides an interesting tool to study the regulation of GAD isoenzymes.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Freichel
authors.forename: H
authors.initials: H
authors.lastname: Potschka
authors.forename: U
authors.initials: U
authors.lastname: Ebert
authors.forename: C
authors.initials: C
authors.lastname: Brandt
authors.forename: W
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D009474:Neurons / Q000378:metabolism*; D009833:Olfactory Pathways / Q000378:metabolism / Q000473:pathology*; D010862:Pilocarpine / Q000633:toxicity; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D020033:Protein Isoforms; D012333:RNA, Messenger; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D007608:Kainic Acid