College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Environ Res. 2015 Feb;137:85-93. doi: 10.1016/j.envres.2014.11.012. Epub 2014 Dec 11.
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.
二氧化硫（SO2）作为一种普遍存在的空气污染物，与肺部疾病的发生有关，现在被认为与神经毒性和脑疾病住院风险增加有关。然而，人们对长期吸入二氧化硫对神经元功能的影响知之甚少。在本研究中，我们通过将雄性 Wistar 大鼠暴露于 3.50 和 7.00 mg/m3 的 SO2（分别约为 EPA 环境空气浓度标准的 1225 和 2450 ppb 的 4.08-8.16 倍）或过滤空气中 90 天，研究了慢性 SO2 吸入对 Morris 水迷宫表现的影响，并探讨了伴随的神经生物学效应，包括活性调节细胞骨架相关基因（Arc）和谷氨酸受体基因表达、记忆相关激酶水平和海马中的炎性细胞因子释放。在这里，我们发现 SO2 暴露减少了目标区穿越次数和目标象限停留时间在空间记忆保留的 Morris 水迷宫测试会议。在神经功能异常之后，我们发现与对照组相比，SO2 吸入以浓度依赖的方式降低了 Arc 和谷氨酸受体亚基（GluR1、GluR2、NR1、NR2A 和 NR2B）的表达。此外，在接受较高浓度的动物中，记忆激酶的表达统计学上减弱，包括蛋白激酶 A（PKA）、蛋白激酶 C（PKC）和钙/钙调蛋白依赖性蛋白激酶 IIα（CaMKIIα）。并且暴露于 SO2 的大鼠炎症细胞因子释放增加。综上所述，我们的结果表明，大鼠长期暴露于高于环境标准的 SO2 空气污染浓度会损害空间学习和记忆能力，并表明大脑中突出的神经生物学变化与行为障碍之间存在密切联系。
