N-Stearoylethanolamine protects the brain and improves memory of mice treated with lipopolysaccharide or immunized with the extracellular domain of a7 nicotinic acetylcholine receptor

• Published in: International immunopharmacology 2017-11, Vol.52, p.290
• Main Authors: Lykhmus, Olena, Uspenska, Kateryna, Koval, Lyudmyla, Lytovchenko, Daria, Voytenko, Larysa, Horid'ko, Tetyana, Kosiakova, Halyna, Gula, Nadiya, Komisarenko, Serhiy, Skok, Maryna
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (nicotinic); Alzheimer's disease; Animal tissues; Apoptosis; Bacteria; Biological activity; Brain; Cognitive ability; Cytochrome; Cytochrome c; IgG antibody; Immunization; Immunoglobulin G; Immunological memory; Inflammation; Interleukin 6; Lipopolysaccharides; Memory; Mice; Mitochondria; Neurodegenerative diseases; Prophylaxis; Receptors; Risk factors; Rodents; β-Amyloid
• ISSN: 1567-5769; 1878-1705

Neuroinflammation is an important risk factor for neurodegenerative disorders like Alzheimer's disease. Nicotinic acetylcholine receptors of a7 subtype (a7 nAChRs) regulate inflammatory processes in various tissues, including the brain. N-stearoylethanolamine (NSE) is a biologically active cell membrane component with anti-inflammatory and membrane-protective properties. Previously we found that mice injected with bacterial lipopolysaccharide (LPS) or immunized with recombinant extracellular domain (1-208) of a7 nAChR subunit possessed decreased a7 nAChR levels, accumulated pathogenic amyloid-beta peptide Aβ(1-42) in the brain and demonstrated impaired episodic memory compared to non-treated mice. Here we studied the effect of NSE on behavior and brain components of LPS- treated or a7(1-208)-immunized mice. NSE, given per os, non-significantly decreased LPS-stimulated interleukin-6 elevation in the brain, slowed down the a7(1-208)-specific IgG antibody production and prevented the antibody penetration into the brain of mice. NSE prevented the loss of a7 nAChRs and accumulation of a7-bound Aβ(1-42) in the brain and brain mitochondria of LPS-treated or a7(1-208)-immunized mice and supported mitochondria resistance to apoptosis by attenuating Ca2 +-stimulated cytochrome c release. Finally, NSE significantly improved episodic memory of mice impaired by either LPS treatment or immunization with a7(1-208). The results of our study demonstrate a therapeutic potential of NSE for prevention of cognitive disfunction caused by neuroinflammation or autoimmune reaction that allows suggesting this drug as a candidate for the treatment or prophylaxis of Alzheimer's pathology.