ABSTRACT
Apolipoproteins in the brain have assumed major clinical importance since it was shown that one of the allelic forms of apolipoprotein E, apoE-4, is a risk factor for Alzheimer's disease. Using tissue culture of embryonic rat spinal cord, we examined the effect of neuronal injury on the up-regulation of two apolipoproteins, apolipoprotein E and clusterin (apoJ). In order to study the influence of neuronal cells, we exploited the specific neurotoxic effect of elevated glutamate on these cells. Overstimulation by excess glutamate induced neuronal degeneration as assessed by morphological and biochemical criteria, notably the activity of choline acetyltransferase, which serves as a marker for cholinergic neurons. High concentrations of glutamate increased mRNA synthesis and the production and secretion of both apolipoprotein E and clusterin protein. Both neuronal cell death and release of the peptides were calcium-dependent and could be blocked by the NMDA receptor antagonist MK-801. Immunohistochemical data revealed the presence of clusterin in both neuronal and non-neuronal cells whereas apolipoprotein E was mainly expressed in non-neuronal cells. The results are suggestive of concerted up-regulation of apolipoprotein E and clusterin when neural cells are subjected to injury.
