Julie Colin

Lipoproteins are natural nanostructures responsible for the transport of cholesterol and other lipids in the blood. They are characterized by having a lipophilic core surrounded by an amphiphilic shell composed of phospholipids, cholesterol and one or more apolipoproteins. Being endogenous carriers makes them suitable for drug delivery purposes. Here, we investigate the effect of lipoproteins’ intricate composition on the entrapment efficiency of a model drug “Cyclosporine A” into the different types of lipoproteins, namely, HDL, LDL and VLDL. It was observed that the protein content of the lipoproteins had the highest effect on the entrapment of the drug with a correlation coefficient of 0.80, 0.81 and 0.96 for HDL, LDL and VLDL respectively. This was even confirmed by the effect of plasma on the association rate of lipoproteins and the drug. The second effective factor is the cholesterol concentration, while triglycerides and phospholipids had a negligible effect.

Polyunsaturated fatty acids play a crucial role in neuronal function, and the modification of these compounds in the brain could have an impact on neurodegenerative diseases such as Alzheimer’s disease. Despite the fact that arachidonic acid is the second foremost polyunsaturated fatty acid besides docosahexaenoic acid, its role and the regulation of its transfer and mobilization in the brain are poorly known. Two groups of 39 adult male BALB/c mice were fed with an arachidonic acid-enriched diet or an oleic acid-enriched diet, respectively, for 12 weeks. After 10 weeks on the diet, mice received intracerebroventricular injections of either NaCl solution or amyloid-β peptide (Aβ) oligomers. Y-maze and Morris water maze tests were used to evaluate short- and long-term memory. At 12 weeks on the diet, mice were killed, and blood, liver, and brain samples were collected for lipid and protein analyses. We found that the administration of an arachidonic acid-enriched diet for 12 weeks induced short-term memory impairment and increased deleterious effects of Aβ oligomers on learning abilities. These cognitive alterations were associated with modifications of expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, postsynaptic density protein 95, and glial fibrillary acidic protein in mouse cortex or hippocampus by the arachidonic acid-enriched diet and Aβ oligomer administration. This diet also led to an imbalance between the main ω-6 fatty acids and the ω-3 fatty acids in favor of the first one in erythrocytes and the liver as well as in the hippocampal and cortical brain structures. In the cortex, the dietary arachidonic acid also induced an increase of arachidonic acid-containing phospholipid species in phosphatidylserine class, whereas intracerebroventricular injections modified several arachidonic acid- and docosahexaenoic acid-containing species in the four phospholipid classes. Finally, we observed that dietary arachidonic acid decreased the expression of the neuronal form of acyl-coenzyme A synthetase 4 in the hippocampus and increased the cytosolic phospholipase A2 activation level in the cortices of the mice. Dietary arachidonic acid could amplify Aβ oligomer neurotoxicity. Its consumption could constitute a risk factor for Alzheimer’s disease in humans and should be taken into account in future preventive strategies. Its deleterious effect on cognitive capacity could be linked to the balance between arachidonic acid-mobilizing enzymes.