CHOLESTEROL-SYNTHESIS AND LIPOPROTEIN REUPTAKE DURING SYNAPTIC REMODELING IN HIPPOCAMPUS IN ADULT-RATS

Apolipoprotein E is synthesized and secreted by astrocytes in the hipp ocampus following lesions of the entorhinal cortex. It was proposed th at apolipoprotein E, by analogy to its role in cholesterol transport i n circulation, could be involved in the salvage and reutilization of n on-esterified cholesterol released during terminal breakdown. The salv aged cholesterol could then be transported to neurons by apolipoprotei n E-complexes and taken up via the apolipoprotein E/apolipoprotein B ( low-density lipoprotein) receptor. To test this hypothesis, we have ex amined low-density lipoprotein receptor binding in brain sections of r ats undergoing hippocampal reinnervation. The number of neuronal cells labelled by fluorescent Dil-low-density lipoprotein as well as the de nsity of [I-125]low-density lipoprotein binding sites in the dentate g yrus were found to increase in parallel with the extent of cholinergic reinnervation occurring in the deafferented hippocampus. In contrast, hippocampal cholesterol synthesis fell by more than 60% at eight days post-lesion, but eventually returned to control levels at 30 days pos t-lesion. The transient loss of cholesterol synthesis coincided with a peak in hippocampal apolipoprotein E expression. A concomitant accumu lation of sudanophilic lipids (cholesterol esters and phospholipids) w as detected in the outer molecular layer of the dentate gyrus and in t he hilar region. The present findings suggest that non-esterified chol esterol released during terminal breakdown is esterified, transported via the apolipoprotein E transport system to neurons undergoing reinne rvation, and take-up through the low-density lipoprotein receptor path way where it is presumably used as a precursor molecule for the synthe sis of new synapses and terminals.