Altered hippocampal expression of calbindin-D-28k and calretinin in GABA(B(1))-deficient mice
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 171621
Author(s) Rüttimann, Elisabeth; Vacher, Claire-Marie; Gassmann, Martin; Kaupmann, Klemens; Van der Putten, Herman; Bettler, Bernhard
Author(s) at UniBasel Bettler, Bernhard
Year 2004
Title Altered hippocampal expression of calbindin-D-28k and calretinin in GABA(B(1))-deficient mice
Journal Biochemical Pharmacology
Volume 68
Number 8
Pages / Article-Number 1613-20
Keywords gamma-aminobutyric acid, GABA(B(1)), epilepsy, knock-out, hippocampus, calcium-binding proteins
Abstract

Balb/c GABA(B(1))(-/-) mice develop complex epileptiform activity, including spontaneous and audiogenic generalized seizures, 6-8 weeks after birth. The neuronal systems involved in these epilepsies have not been identified yet. Because the hippocampus is critically involved in epileptiform activity, we now investigated whether this brain region exhibits seizure-related alterations. Using semi-quantitative immunohistochemistry, we studied the temporal and cellular hippocampal expression pattern of two seizure-sensitive calcium-binding proteins, calbindin-D-28k and calretinin, in GABA(B(1))(-/-) mice. One month after birth, before the onset of overt epileptiform activity, wild-type (WT) and GABA(B(1))(-/-) mice exhibit comparable expression profiles for the two calcium-binding proteins. Three months after birth, once the epileptic phenotype is established, we observe clear alterations in the expression of calcium-binding proteins in the dentate gyrus area. GABA(B(1))(-/-) mice exhibit a 50% decline in the staining intensity of calbindin-D-28k expressing neurons and a 70% increase in the number of calretinin-positive neurons when compared to WT littermates. Six months after birth, the down-regulation of calbindin-D-28k protein is even more pronounced, while the calretinin expression in GABA(B(1))(-/-) mice reverts to the pattern seen in WT littermates. Our data demonstrate that the absence of functional GABA(B) receptors causes epileptiform activity through a mechanism that crucially involves dentate gyrus granule cells, and that this pathological activity is accompanied by adaptive changes.

Publisher Pergamon Press
ISSN/ISBN 0006-2952
edoc-URL http://edoc.unibas.ch/dok/A5262244
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.bcp.2004.07.019
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/15451404
ISI-Number WOS:000224809000016
Document type (ISI) Journal Article
 
   

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