INJURY-INDUCED SYNTHESIS AND RELEASE OF APOLIPOPROTEIN-E AND CLUSTERIN FROM RAT NEURAL CELLS

Apolipoproteins in the brain have assumed major clinical importance si nce it was shown that one of the allelic forms of apolipoprotein E, ap oE-4, is a risk factor for Alzheimer's disease. Using tissue culture o f embryonic rat spinal cord, we examined the effect of neuronal injury on the up-regulation of two apolipoproteins, apolipoprotein E and clu sterin (apoJ). In order to study the influence of neuronal cells, we e xploited the specific neurotoxic effect of elevated glutamate on these cells. Overstimulation by excess glutamate induced neuronal degenerat ion as assessed by morphological and biochemical criteria, notably the activity of choline acetyltransferase, which serves as a marker for c holinergic neurons. High concentrations of glutamate increased mRNA sy nthesis and the production and secretion of both apolipoprotein E and clusterin protein. Both neuronal cell death and release of the peptide s were calcium-dependent and could be blocked by the NMDA receptor ant agonist MK-801. Immunohistochemical data revealed the presence of clus terin in both neuronal and non-neuronal cells whereas apolipoprotein E was mainly expressed in non-neuronal cells. The results are suggestiv e of concerted up-regulation of apolipoprotein E and clusterin when ne ural cells are subjected to injury.