ROLE OF LIPOPROTEINS IN THE DELIVERY OF LIPIDS TO AXONS DURING AXONALREGENERATION

Nerve fiber elongation involves the input of lipids to the growing axo ns. Since cell bodies are often a great distance from the regenerating tips, alternative sources of lipids have been proposed. We previously demonstrated that axonal synthesis of phosphatidylcholine is required for axonal growth (Posse de Chaves, E., Vance, D. E., Campenot, R. B. and Vance, J. E. (1995) J. Cell Biol, 128, 913-918; Posse de Chaves, E., Vance, D. E., Campenot, R. B. and Vance, J. E. (1995) Biochem, J. 312, 411-417), In contrast, cholesterol is not made in axons. We now s how that when compartmented cultures of rat sympathetic neurons are in cubated with pravastatin, in the absence of exogenously supplied lipid s, cholesterol synthesis is inhibited and axonal growth is impaired. T he addition of cholesterol to the axons or cell bodies of neurons trea ted with this inhibitor restores normal axonal elongation. Similarly, a supply of cholesterol via lipoproteins restores normal axonal growth . In contrast, lipoproteins do not provide axons with sufficient phosp hatidylcholine for normal elongation when axonal phosphatidylcholine s ynthesis is inhibited. Thus, our studies support the idea that during axonal regeneration lipoproteins can be taken up by axons from the mic roenvironment and supply sufficient cholesterol, but not phosphatidylc holine, for growth, We also show that neither apoE nor apoA-I within t he lipoproteins is essential for axonal growth.