Dissociation of apolipoprotein and apolipoprotein receptor response to lesion in the rat brain: an in situ hybridization study.

The epsilon4 allele of apolipoprotein E is associated with increased risk for developing Alzheimer's disease. To further understand the anatomical distribution of apolipoprotein E and its native receptors in the brain, we studied their messenger RNA expression in the adult rat brain under normal conditions and in response to an excitotoxic lesion to the hippocampus. In situ hybridization using oligonucleotide probes for apolipoprotein E, apolipoprotein J, the low density lipoprotein receptor, very low density lipoprotein receptor, low density lipoprotein receptor related protein, 39,000 mol. wt receptor-associated protein and glycoprotein 330/Megalin messenger RNA were performed on adjacent sections throughout the rat forebrain. Apolipoprotein E messenger RNA was abundantly expressed in the rat brain in both white and gray matter localizing to astrocytes but not neurons. Low density lipoprotein receptor-related protein and receptor-associated protein messenger RNA had a similar regional distribution but low density lipoprotein receptor-related protein messenger RNA was expressed by both neurons and glia, while the expression of receptor-associated protein messenger RNA was more highly expressed in neurons. Apolipoprotein J messenger RNA was expressed by neurons, glia and choroid plexus. The low density lipoprotein receptor and very low density lipoprotein receptor messenger RNA were found in both neurons and glia. Glycoprotein 330/Megalin messenger RNA was not detectable in the adult rat brain. In response to hippocampal lesions, apolipoprotein E and apolipoprotein J messenger RNAs were significantly up-regulated seven and 11 days post-lesion but the expression of low density lipoprotein receptor, low density lipoprotein receptor-related protein, receptor-associated protein, glycoprotein 330/Megalin, and very low density lipoprotein receptor messenger RNAs were unchanged. The expression of apolipoprotein E messenger RNA increased gradually beginning at three days while the expression of apolipoprotein J messenger RNA began to increase at seven days post-lesion. These findings further implicate apolipoproteins in the response of the brain to injury in vivo and suggest that transcriptional up-regulation of the apolipoprotein receptors studied is not a prominent feature in the response.