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 alterations of the hippocampal formation was assessed in single- and double-knockout mice, using a kainate model of mesial temporal lobe epilepsy. The effects of a unilateral intrahippocampal injection of kainic acid were assessed at one day, 30 days, and four months post-injection, using various markers of GABAergic interneurons (GABA-transporter type 1, GABA(A)-receptor alpha1 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 the hippocampal formation and in the number, distribution, or morphology of interneurons 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 neurochemical alterations (e.g., bilateral induction of neuropeptide Y in granule cells) and morphogenic changes (enlargement and dispersion of dentate gyrus granule cells) as wild-type animals. Quantification of interneurons revealed no 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 interneurons. Furthermore, they are not protective against kainate-induced excitotoxicity in this model, and do not appear to modulate the overall level of excitability of the hippocampus. Finally, seizure-induced changes in gene expression in granule cells, which normally express high levels of calcium-binding proteins, apparently were not affected by the gene deletions analysed.
Bouilleret
V
V
INSERM U. 398, Faculté de Médecine, 11 rue Humann, 67085, Strasbourg, France.
Schwaller
B
B
Schurmans
S
S
Celio
M R
MR
Fritschy
J M
JM
D000818:Animals; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000032:analysis / Q000378:metabolism; D027361:Organic Anion Transporters; D010320:Parvalbumins / Q000032:analysis / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013004:Somatostatin / Q000032:analysis / Q000378:metabolism
C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009478:Neuropeptide Y; D027361:Organic Anion Transporters; D010320:Parvalbumins; D011963:Receptors, GABA-A; D064030:S100 Calcium Binding Protein G; D013004:Somatostatin; D007608:Kainic Acid