Uptake of lipoproteins for axonal growth of sympathetic neurons

Lipoproteins originating from axon and myelin breakdown in injured peripher al nerves are believed to supply cholesterol to regenerating axons. We have used compartmented cultures of rat sympathetic neurons to investigate the utilization of lipids from lipoproteins for axon elongation. Lipids and pro teins from human low density lipoproteins (LDL) and high density lipoprotei ns (HDL) were taken up by distal axons and transported to cell bodies, wher eas cell bodies/proximal axons internalized these components from only LDL, not HDL. Consistent with these observations, the impairment of axonal grow th, induced by inhibition of cholesterol synthesis, was reversed when LDL o r HDL were added to distal axons or when LDL, but not HDL, were added to ce ll bodies. LDL receptors (LDLRs) and LR7/8B (apoER2) were present in cell b odies/proximal axons and distal axons, with LDLRs being more abundant in th e former. Inhibition of cholesterol biosynthesis increased LDLR expression in cell bodies/proximal axons but not distal axons. LR11 (SorLA) was restri cted to cell bodies/proximal axons and was undetectable in distal axons, Ne ither the LDL receptor-related protein nor the HDL receptor, SR-B1, was det ected in sympathetic neurons. These studies demonstrate for the first time that lipids are taken up from lipoproteins by sympathetic neurons for use i n axonal regeneration.