科研之友
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摘要
Nicotinic acetylcholine receptors (nAChRs) expressed in the brain are involved in regulating cognitive functions, as well as inflammatory reactions. Their density is decreased upon Alzheimer disease accompanied by accumulation of beta-amyloid (A beta(42)), memory deficit and neuroinflammation. Previously we found that alpha 7 nAChR-specific antibody induced proinflammatory interleukin-6 production in U373 glioblastoma cells and that such antibodies were present in the blood of humans. We raised a hypothesis that alpha 7 nAChR-specific antibody can cause neuroinflammation when penetrating the brain. To test this, C57Bl/6 mice were either immunized with extracellular domain of alpha 7 nAChR subunit alpha 7(1-208) or injected with bacterial lipopolysaccharide (LPS) for 5 months. We studied their behavior and the presence of alpha 3, alpha 4, alpha 7, beta 2 and beta 4 nAChR subunits, A beta(40) and A beta(42) and activated astrocytes in the brain by sandwich ELISA and confocal microscopy. It was found that either LPS injections or immunizations with alpha 7(1-208) resulted in region-specific decrease of alpha 7 and alpha 4 beta and increase of alpha 3 beta 4 nAChRs, accumulation of A beta(42) and activated astrocytes in the brain of mice and worsening of their episodic memory. Intravenously transferred alpha 7 nAChR-specific-antibodies penetrated the brain parenchyma of mice pre-injected with LPS. Our data demonstrate that (1) neuroinflammation is sufficient to provoke the decrease of alpha 7 and alpha 4 beta 2 nAChRs, A beta(42) accumulation and memory impairment in mice and (2) alpha 7(1-208) nAChR-specific antibodies can cause inflammation within the brain resulting in the symptoms typical for Alzheimer disease.
- 出版日期2015-3-27
