Df. Condorelli et al., CHANGES IN GENE-EXPRESSION OF AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBUNITS INDUCED BY STATUS EPILEPTICUS IN RAT-BRAIN, Neurochemistry international, 25(4), 1994, pp. 367-376
In the present investigation we address the question of whether one of
the responses to increased neuronal activity is a modification of the
expression of the different subunits of alpha-amino-3-hydroxy-5-methy
l-4-isoxazole propionate (AMPA)-selective glutamate receptors (GluR-1,
GluR-2, GluR-3). Thus, we used two different models of generalized st
atus epilepticus, as widespread elevated neuronal activity, to study i
n vivo responses of the AMPA receptor mRNA expression in rat forebrain
. By Northern blot analysis and in situ hybridization, we show that on
e of the delayed responses to LiCl/pilocarpine-induced status epilepti
cus is a dramatic change in the mRNA level of some subunits of AMPA-se
lective glutamate receptors. These effects, which appear between 6 and
12 h after the drug treatment, are subunit and brain region specific.
The most striking example of differential expression of the three exa
mined GluR mRNAs can be observed in the dentate gyrus of the hippocamp
us. In this specific brain subregion an increase of GluR-3 mRNA level
is induced 12 h after LiCl/pilocarpine treatment, while a clear decrea
se in GluR-1 mRNA level and no significant change in GluR-2 mRNA level
can be observed in the same area under these experimental conditions.
Both the GluR-1 decrease and the GluR-3 increase are transient effect
s and a return to basal level can be observed after 48-72 h. In the CA
1 layer of the hippocampus, a parallel decrease of both GluR-1 and Glu
R-3 expression is found 12-24 h after drug treatment, followed by a re
covery of the expression to control values at 48 h. In kainate-induced
epilepsy we could reproduce the late increase (12-24 h) in GluR-3 mRN
A in the dentate gyrus;however, under this experimental condition, no
clear decrease of GluR-1 expression can be observed in this area. A ge
neral decrease in mRNA level for the AMPA receptor subunits (GluR-1-3)
in the hippocampal layers, in particular in CA3 and CA4 subfields, wa
s also observed. In conclusion the results reported in the present pap
er reveal a specific regulation of GluR gene expression in the granule
cells of the hippocampal dentate gyrus and stimulate further investig
ation on the functional role of the GluR-3 subunit in the receptor-cha
nnel complex.