Neuroinflammation is an important risk factor for neurodegenerative disorders like Alzheimer's disease. Nicotinic acetylcholine receptors of α7 subtype (α7 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 α7 nAChR subunit possessed decreased α7 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 α7(1-208)-immunized mice. NSE, given per os, non-significantly decreased LPS-stimulated interleukin-6 elevation in the brain, slowed down the α7(1-208)-specific IgG antibody production and prevented the antibody penetration into the brain of mice. NSE prevented the loss of α7 nAChRs and accumulation of α7-bound Aβ(1-42) in the brain and brain mitochondria of LPS-treated or α7(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 α7(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.
Keywords: Alzheimer disease; Mitochondria; N-stearoylethanolamine; Neuroinflammation; α7 nicotinic acetylcholine receptor.
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