Modulation of apolipoprotein D and apolipoprotein E expression in rat hippocampus after entorhinal cortex lesion

Apolipoprotein (apo) D is a member of the lipocalin family of proteins. Alt hough its physiological function is unknown, apoD is thought to transport o ne or more small hydrophobic ligands. A second apolipoprotein, apoE is know n to play an important role in lipid transport, and apoE genetic polymorphi sm has been shown to be associated with susceptibility to Alzheimer's disea se. Both apoD and apoE are expressed in the central nervous system (CNS) an d both proteins accumulate at sites of peripheral nerve injury due to incre ased local synthesis. The two proteins may have overlapping or complementar y functions within nervous tissue. in order to define the role of apoD with in the CNS, we have studied the regional distribution of apoD and apoE mRNA and protein within the normal rat brain and the changes in apoD and apoE e xpression in the hippocampus of rats after entorhinal cortex lesion (EC les ion). Within the brains of normal rats, apoD expression in the hippocampus was as high as 180-fold that of the liver. ApoD mRNA levels in other areas of the rat brain ranged from 40 to 120 times the hepatic levels. The distri bution of apoE gene expression within the brain was similar to that of apoD , but was much lower than hepatic apoE expression. When rats were subjected to EC lesion, the apoD message increased by 54% at 4 days post lesion (DPL ) in the ipsilateral region of hippocampus while apoE mRNA levels (ipsilate ral and contralateral) decreased by 43%. At 6 to 8 DPL apoD mRNA in the ips ilateral hippocampus remained elevated (42% above controls) whereas the apo E mRNA levels increased to about 15% above those of controls. At 14 and 31 DPL, both apoD and apoE expression was similar to controls. The increase in immunoreactive apoD in hippocampal extracts was more dramatic. At 1 DPL, i mmunoreactive apoD levels were already 16-fold higher than those in extract s of non-lesioned animals and, at 31 DPL, levels were still 8-fold higher t han those of control animals. Finally, we have demonstrated that the levels of apoD in the brains of apoE-deficient mice are 50-fold those of wildtype control mice. ApoD clearly has an important function within the CNS in bot h normal and pathological situations. (C) 1999 Elsevier Science B.V. All ri ghts reserved.