title: NO2 inhalation promotes Alzheimer's disease-like progression: cyclooxygenase-2-derived prostaglandin E2 modulation and monoacylglycerol lipase inhibition-targeted medication.
abstract: Air pollution has been reported to be associated with increased risks of cognitive impairment and neurodegenerative diseases. Because NO2 is a typical primary air pollutant and an important contributor to secondary aerosols, NO2-induced neuronal functional abnormalities have attracted greater attention, but the available experimental evidence, modulating mechanisms, and targeting medications remain ambiguous. In this study, we exposed C57BL/6J and APP/PS1 mice to dynamic NO2 inhalation and found for the first time that NO2 inhalation caused deterioration of spatial learning and memory, aggravated amyloid β42 (Aβ42) accumulation, and promoted pathological abnormalities and cognitive defects related to Alzheimer's disease (AD). The microarray and bioinformation data showed that the cyclooxygenase-2 (COX-2)-mediated arachidonic acid (AA) metabolism of prostaglandin E2 (PGE2) played a key role in modulating this aggravation. Furthermore, increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented PGE2 production, neuroinflammation-associated Aβ42 accumulation, and neurodegeneration, indicating a therapeutic target for relieving cognitive impairment caused by NO2 exposure.
authors.affiliation: College of Environment and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: College of Environment and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yun
authors.affiliation: College of Environment and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ku
authors.affiliation: College of Environment and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Guangke
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Environment and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000397:Air Pollution / Q000009:adverse effects; D000544:Alzheimer Disease / Q000139:chemically induced*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D002853:Chromatography, Liquid; D060825:Cognitive Dysfunction / Q000139:chemically induced*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism; D005989:Glycerides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010446:Peptide Fragments / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects*; D053719:Tandem Mass Spectrometry
chemical_list: D016229:Amyloid beta-Peptides; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016718:Arachidonic Acid; C094503:glyceryl 2-arachidonate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D008994:Monoacylglycerol Lipases; D015232:Dinoprostone; D009585:Nitrogen Dioxide