NERVE REGENERATION AND CHOLESTEROL REUTILIZATION OCCUR IN THE ABSENCEOF APOLIPOPROTEIN-E AND APOLIPOPROTEIN-A-I IN MICE

Apolipoproteins have been implicated in the salvage and reutilization of myelin cholesterol during Wallerian degeneration and the subsequent nerve regeneration. Current evidence suggests that myelin cholesterol complexes with apolipoproteins E and A-l to form lipoproteins that ar e taken up via low-density lipoprotein receptors on myelinating Schwan n cells. We recently reported, however, that apolipoprotein E is not r equired for nerve regeneration or reutilization of myelin cholesterol. We have now investigated nerve regeneration and the reutilization of cholesterol in mutant mice deficient in both apolipoproteins E and A-l . Morphologic examination of nerves 4 and 12 weeks after crush injury revealed that regeneration proceeded at a normal rate in the absence o f these apolipoproteins. Autoradiography of regenerating nerves indica ted that prelabeled myelin lipid was reutilized in the regenerating my elin. 3-Hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzy me in cholesterol synthesis, was down-regulated in the regenerating ne rves, indicative of cholesterol uptake via lipoproteins. Prelabeled my elin cholesterol was present in lipoprotein fractions isolated from cr ushed nerves of mutant mice. These data suggest that there is consider able redundancy in the process of cholesterol reutilization within ner ve, and that apolipoproteins other than apolipoproteins E and A-I may be involved in the recycling of myelin cholesterol.