title: Chronic SO2 inhalation above environmental standard impairs neuronal behavior and represses glutamate receptor gene expression and memory-related kinase activation via neuroinflammation in rats.
abstract: Sulfur dioxide (SO2), as a ubiquitous air pollutant implicated in the genesis of pulmonary disease, is now being considered to be involved in neurotoxicity and increased risk for hospitalization of brain disorders. However, comparatively little is known about the impact of chronically SO2 inhalation on neuronal function. In the present study, by exposing male Wistar rats to SO2 at 3.50 and 7.00 mg/m(3) (approximately 1225 and 2450 ppb, 4.08-8.16 (24h average concentration) times higher than the EPA standard for environmental air concentrations) or filtered air for 90 days, we investigated the impact of chronic SO2 inhalation on performance in Morris water maze, and probed the accompanying neurobiological effects, including activity-regulated cytoskeletal associated gene (Arc) and glutamate receptor gene expression, memory-related kinase level and inflammatory cytokine release in the hippocampus. Here, we found that SO2 exposure reduced the number of target zone crossings and time spent in the target quadrant during the test session in the spatial memory retention of the Morris water maze. Following the neuro-functional abnormality, we detected that SO2 inhalation reduced the expression of Arc and glutamate receptor subunits (GluR1, GluR2, NR1, NR2A, and NR2B) with a concentration-dependent property in comparison to controls. Additionally, the expression of memory kinases was attenuated statistically in the animals receiving the higher concentration, including protein kinase A (PKA), protein kinase C (PKC) and calcium/calmodulin-dependent protein kinaseIIα (CaMKIIα). And the inflammatory cytokine release was increased in rats exposed to SO2. Taken together, our results suggest that long-term exposure to SO2 air pollution at concentrations above the environmental standard in rats impaired spatial learning and memory, and indicate a close link between the neurobiological changes highlighted in the brain and the behavioral disturbances.
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Gaoyi
authors.initials: G
authors.lastname: Yao
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Yue
authors.affiliation: College of Environment and Resource, 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 Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China. Electronic address: sangnan@sxu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019570:Inhalation Exposure; D008297:Male; D008568:Memory / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D065853:Spatial Learning / Q000187:drug effects*; D013458:Sulfur Dioxide / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D013458:Sulfur Dioxide
keywords: Activity-regulated cytoskeletal gene (Arc); Glutamate receptor; Neuro-inflammatory cytokine; SO(2) inhalation; Spatial learning and memory