[Gel-forming mucins structure governs mucus gels viscoelasticity]. / La structure des mucines conditionne les propriétés viscoélastiques des gels de mucus.

Mucus is the first line of innate mucosal defense in all mammals. Gel­forming mucins control the rheological properties of mucus hydrogels by forming a network in which hydrophilic and hydrophobic regions coexist, and it has been revealed that the network is formed through both covalent links and reversible links such as hydrophobic interactions in order to modulate the structure as a function of the physiological necessities. Here, we review the structure and functions of the mucus in terms of the gel-forming mucins protein-protein interactions, also called interactome. Since it is difficult to characterize the low energy reversible interactions due to their dependence on physico-chemical environment, their role is not well understood. Still, they constitute a promising target to counteract mucus abnormalities observed in mucus-associated diseases.

Dietary arachidonic acid increases deleterious effects of amyloid-ß oligomers on learning abilities and expression of AMPA receptors: putative role of the ACSL4-cPLA2 balance.

BACKGROUND: 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. METHODS: 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-ß peptide (Aß) 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. RESULTS: We found that the administration of an arachidonic acid-enriched diet for 12 weeks induced short-term memory impairment and increased deleterious effects of Aß 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 Aß 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. CONCLUSIONS: Dietary arachidonic acid could amplify Aß 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.

In vivo imaging of the Muc5b gel-forming mucin.

Gel-forming mucins are macromolecules produced by goblet cells and responsible for the mucus gel formation. Changes in goblet cell density and in gel-forming mucin production have emerged as sensitive indicators for mucosal diseases. A Muc5b-GFP tagged reporter mouse was used to assess Muc5b production in mouse tissues by immunofluorescence microscopy and fluorescent activity using stereromicroscopy and probe-based confocal laser endomicroscopy. Muc5b production was followed longitudinally by recording the fluorescent activity in vagina and in embryonic lung explants under stimulation by interleukin 13. We show that the GFP is easily visualized in the mouse adult ear, nose, trachea, gallbladder, and cervix. Live Muc5b is also easily monitored in the nasal cavity, trachea and vagina where its production varies during the estrus cycle with a peak at the proestrus phase and in pregnant mice. Explant culture of reporter mouse embryonic whole lung shows that interleukin 13 stimulates Muc5b production. The transgenic Muc5b-GFP mouse is unique and suitable to study the mechanisms that regulate Muc5b production/secretion and mucous cell differentiation by live imaging and can be applied to test drug efficacy in mucosal disease models.