Clusterin accumulates in dying neurons following status epilepticus

Clusterin is a protein that has been implicated in cell death and remodelling in a number of different tissues. To further investigate the role of clusterin in nerve cell death its expression was measured in the rat brain at various times after status epilepticus (SE) induced by 1 h of hippocampal stimulation, by using in situ hybridization, immunocytochemistry, and immunoblotting. SE lead to a dramatic time-dependent increase in clusterin mRNA in non-nerve cells resembling astrocytes in the hippocampus beginning after 24 h. There was also an earlier induction of clusterin mRNA in dentate granule cells, that survive SE. Only a low mRNA signal was observed over the CA1 pyramidal cells, which die after SE. In contrast to these mRNA results, massive clusterin-like immunoreactivity was observed in CA1 pyramidal cells and dentate hilar neurons (and both of these neuronal populations die after SE), but not in dentate granule cells. We speculate that astrocytes produce clusterin after SE and that the clusterin is then secreted and taken up by hippocampal neurons destined to die. Thus, the role of clusterin in nerve cell death/ regeneration warrants further investigation.