Distribution of perlecan in mouse hippocampus following intracerebroventricular kainate injections

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.