Wy. Ong et al., AN IMMUNOCYTOCHEMICAL STUDY OF GLUTAMATE RECEPTORS AND GLUTAMINE-SYNTHETASE IN THE HIPPOCAMPUS OF RATS INJECTED WITH KAINATE, Experimental Brain Research, 109(2), 1996, pp. 251-267
Immunocytochemistry was used to study the distribution of the kainate
receptors GluR1, GluR2/3 and GluR4 and of the N-methyl-D-aspartate (NM
DA) receptor NMDAR1 as well as the astrocyte markers glutamine synthet
ase (GS) and glial fibrillary acidic protein (GFAP) in the hippocampus
of normal and kainate-lesioned rats. Hippocampal pyramidal neurons an
d dentate granule neurons were labelled heavily for GluR1 and GluR2/3,
but only lightly for GluR4. Dense GluR4 immunopositivity was, however
, observed in oligodendrocyte-like glial cells. Hippocampal pyramidal
neurons and dentate granule neurons were moderately labelled for NMDAR
1. Intravenous kainate injections resulted in a decrease in GluR1 and
GluR2/3 immunoreactivity on the apical dendrites of pyramidal neurons
as early as 7 h postinjection. At 18 h, there was a marked reduction i
n GluR1 and GluR2/3 receptors in the terminal tuft of dendrites of mos
t hippocampal pyramidal neurons in the affected area, although some ce
lls showed labelling in other portions of the apical dendrites and in
basal dendrites. Immunostaining for GluR4 and NMDAR1 was also reduced
at this time. At postinjection day 3, only the cell bodies and the bas
al dendrites of a few scattered pyramidal cells were labelled. Taken t
ogether, these results indicate a progressive loss of glutamate recept
ors, which affects the apical dendritic tree before the basal dendriti
c tree. The decrease in receptor immunoreactivity could be due to a do
wnregulation of the receptors, since it occurred as early as 7 h postl
esion, before cell death was evident in Nissl-stained sections. At lon
g intervals after kainate injection, all pyramidal cells at the centre
of the lesion showed a lack of glutamate receptor staining, and no pa
rtially labelled pyramidal cells were observed. The periphery of the l
esion, however, contained many partially labelled pyramidal neurons am
ong the unlabelled cells and had features of early lesions. The presen
t study also showed an early decrease in GS immunoreactivity in the af
fected CA fields of the hippocampus (18 h to 3 days postinjection), fo
llowed by a medium-term increase (5-68 days) and a late decrease in GS
immunoreactivity (81 days). The decrease in GS immunoreactivity at 81
days is not due to an absence of astrocytes, since GFAP staining show
ed many densely labelled astrocytes in the affected CA field.