Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin

The functional role of the calcium-binding proteins parvalbumin, calretinin , and calbindin D-28k for epileptogenesis and long-term seizure-related alt erations of the hippocampal formation was assessed in single- and double-kn ockout mice, using a kainate model of mesial temporal lobe epilepsy. The ef fects of a unilateral intrahippocampal injection of kainic acid were assess ed at one day, 30 days, and four months post-injection, using various marke rs of GABAergic interneurons (GABA-transporter type 1, GABA(A)-receptor alp ha 1 subunit, calretinin, calbindin D-28k, somatostatin, and neuropeptide Y ). Parvalbumin-deficient, parvalbumin/calbindin-deficient, and parvalbumin/ calretinin-deficient mice exhibited no difference in cytoarchitecture of th e hippocampal formation and in the number, distribution, or morphology of i nterneurons compared to wild-type mice. Likewise, mutant mice were not more vulnerable to acute kainate-induced excitotoxicity or to long-term effects of recurrent focal seizures, and exhibited the same pattern of neurochemic al alterations (e.g., bilateral induction of neuropeptide Y in granule cell s) and morphogenic changes (enlargement and dispersion of dentate gyrus gra nule cells) as wild-type animals. Quantification of interneurons revealed n o significant difference in neuronal vulnerability among the genotypes. These results indicate that the calcium-binding proteins investigated here are not essential for determining the neurochemical phenotype of interneuro ns. Furthermore, they are not protective against kainate-induced excitotoxi city in this model, and do not appear to modulate the overall level of exci tability of the hippocampus. Finally, seizure-induced changes in gene expre ssion in granule cells, which normally express high levels of calcium-bindi ng proteins, apparently were not affected by the gene deletions analysed. ( C) 2000 IBRO. Published by Elsevier Science Led.