P. Montpied et al., ALTERATION IN LEVELS OF EXPRESSION OF BRAIN CALBINDIN D-28K AND CALRETININ MESSENGER-RNA IN GENETICALLY EPILEPSY-PRONE RATS, Epilepsia, 36(9), 1995, pp. 911-921
Variations in the concentration of free calcium in neurons is believed
to play a major role in regulating neuronal excitability. Because cal
cium-binding proteins such as calbindin D-28k. and calretinin help to
regulate intracellular calcium, we: investigated the possibility that
the expression of these proteins may be affected in genetically epilep
sy-prone rats (GEPRs). The mRNA levels of both proteins were compared
across several brain regions using in situ hybridization histochemistr
y and Northern blot analysis with semiquantitation by optical density
measures on autoradiograms from two GEPR strains that differ in the se
verity of audiogenic seizures (GEPR9 and GEPR3) and from Sprague-Dawfe
y rats. Results revealed a lower level of expression in calbindin D-28
k mRNA in the caudate putamen-accumbens nuclei in GEPR3 (-30%) and GEP
R9 (-60%) relative to controls, The calbindin D-28k mRNA level was als
o lower in the reuniens nucleus of the thalamus (-41% in GEPR3; - 34%
in GEPR9). The calretinin mRNA level was lower in the substantia nigra
compacta of both GEPR rat strains (-31% in GEPR3 and -34% in GEPR9 re
lative to controls). No changes in mRNA were detected in other brain r
egions expressing calbindin D-28k or calretinin mRNA. These results in
dicate that the expression of these related calcium-binding proteins i
s altered in the GEPRs before the induction of seizures. This initial
defect could alter either the calcium-buffering capacity or regulation
of calcium-mediated processes by these proteins and thus play a role
in the molecular cascade of events inducing the genetic susceptibility
to, and the generalization of, seizures in these rat strains.