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Volume 272, Number 49, Issue of December 5, 1997 pp. 30766-30773
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Role of Lipoproteins in the Delivery of Lipids to Axons during Axonal Regeneration

(Received for publication, June 16, 1997, and in revised form, September 11, 1997)

Elena I. Posse de Chaves ^§ , Antonio E. Rusiñol ^§ , Dennis E. Vance , Robert B. Campenot and Jean E. Vance ^§

From the  Lipid and Lipoprotein Research Group and the Departments of  Biochemistry,  Cell Biology and Anatomy, and ^§ Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

Nerve fiber elongation involves the input of lipids to the growing axons. 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 show that when compartmented cultures of rat sympathetic neurons are incubated with pravastatin, in the absence of exogenously supplied lipids, cholesterol synthesis is inhibited and axonal growth is impaired. The addition of cholesterol to the axons or cell bodies of neurons treated 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 phosphatidylcholine for normal elongation when axonal phosphatidylcholine synthesis is inhibited. Thus, our studies support the idea that during axonal regeneration lipoproteins can be taken up by axons from the microenvironment and supply sufficient cholesterol, but not phosphatidylcholine, for growth. We also show that neither apoE nor apoA-I within the lipoproteins is essential for axonal growth.

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