Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain

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Our team has documented an elegant mechanism by which the injured brain uses the cholesterol and phospholipids released from dead/dying cells to feed surviving neurons with the lipids which are required for the proper rebuilding new synaptic networks. We call this process the cholesterol recycling/remodeling cascade. Our team has already demonstrated that the extracellular transport of cholesterol and phospholipids by apolipoprotein E (apoE), a highly functional lipid transporter, is required and necessary for the replacement of synaptic networks in response to brain injury or, neurotoxic insult in rodents. In response, cell-surface receptors that recognize apoE-lipoprotein complexes (i.e. HDL) were found to mediate the internalization and redistribution of the cholesterol required for the formation of new sprouts and new synapses. The complete absence of brain apoE or, its main receptor, in knockout mice was shown to compromise i) synaptic integrity with age, ii) lesion-induced synaptic recovery and iii) cognitive performance. Unfortunately, we know very little about the initiation of this cascade; i.e. the transport and packaging of cholesterol and phospholipids from intracellular astroglial compartments towards the apoE-lipoprotein (HDL) assembly line.