The distribution of the heparan sulphate
proteoglycan (
HSPG),
perlecan, was studied by immunocytochemistry in the normal mouse hippocampus after intracerebroventricular
injections of the potent
convulsant and
neurotoxin,
kainate. A light staining to
perlecan was observed in neurons in the normal hippocampus. Following
kainate injection, an increase in
perlecan immunoreactivity was observed in degenerating neurons from one to three post-injection days, followed by glial cells from 5 days to 4 weeks post-injection. The latter were found at electron microscopy to contain light cytoplasm and dense bundles of glial filaments, and had features of viable reactive astrocytes. Some endothelial cells were also labelled. The significance of an increased expression of
perlecan in the injured hippocampus is unknown. One possibility, in view of observations that
HSPG promotes neurite outgrowth [A.D. Lander, D.K. Fujii, D. Gospodarowicz, L.F. Reichardt, Characterization of
a factor that promotes neurite outgrowth: evidence linking neurite activity to a
heparan sulfate proteoglycan, J. Cell Biol. 94 (1982) 574-585] is that
perlecan enhances the early stages of brain tissue regeneration. It is, however, speculated that such growth promoting activity may ordinarily be suppressed, due to concurrent increased expression of other
proteoglycans such as the NG2
chondroitin sulphate
proteoglycan, which are inhibitory to neurite outgrowth [C. Dou, J.M. Levine, Inhibition of neurite outgrowth by the NG2
chondroitin sulfate proteoglycan, J. Neurosci. 14 (1994) 7616-7628]. It is also possible that a similar increased expression of
perlecan in neurons and reactive astrocytes could occur in humans following neuronal injury, which could be a source of
perlecan, in
senile plaques of
Alzheimer's disease.