CNS Toxicity Induced by DEPs and Ambient Particles
Date Issued
2016
Date
2016
Author(s)
Wu, Yi-Ling
Abstract
Epidemiological and toxicological studies have shown that particulate matter (PM) may have adverse effects on the central nervous system (CNS). However, the underlying mechanisms remain unclear. Therefore, we conducted an experiment to explore the CNS toxicity induced by PM. In the first experiment, 8-week old male C57BL/6J mice were exposed to diesel exhaust particles (DEPs) by intratracheal instillation (I.T.) twice within two weeks. PBS (control group), 50μg DEPs (total 100μg DEPs group) or DEPs 150μg DEPs (total 300μg DEPs group) were administered. In the second experiment, C57BL/6J mice were exposed to ambient air by inhalation for about 3 months from the age of 4-weeks. The control group was given HEPA-filtered air. MWM test were conducted to evaluate spatial learning and memory. In above experiments, Morris water maze (MWM) test was conducted to test the capacity of spatial learning and memory. Inflammatory cytokines including IL-1β, IL-6, TNF-α and oxidative stress marker of 8-OHdG and 8-NO2Gua were determined. In the acute study, the median of escape latency in the total 300μg DEPs group was significantly longer than the control group in the fourth day (35.4 seconds vs. 14.2 seconds, P=0.036, Kruskal-Wallis test). In olfactory bulb (OB) and cerebellum (CE), the level of TNF-α was increased. The level of IL-1β was increased in CE, cerebral medulla (ME) and cortex (CO). The level of IL-6 was increased in ME and CO. In the inhalation study with healthy mice, the median of escape latency in the exposure group was significantly longer than the control group in the third day (45.1 seconds vs. 27.6 seconds, p=0.018, Wilcoxon rank sum test). Level of IL-1β and IL-6 were increased in the control group in CE. Level of IL-1β was increased in the control group in hippocampus (HI). 8-OHdG significantly increased in OB, CE, ME, HI and CO and 8-NO2Gua significantly increased in HI. Our results showed that acute exposure to DEPs caused poor spatial learning and increases the level of pro-inflammatory in different brain partitions. Sub-chronic exposure to ambient particles also causes adverse effects on behavior performance. However, the pro-inflammatory cytokines were not increased. 8-OHdG and 8-NO2Gua in healthy young adult mice were increased. Sub-chronic exposure to non-concentrated ambient particles may have adverse effects on spatial learning by accumulation of oxidative stress in CNS.
Subjects
ambient particles
diesel exhaust particles
Morris water maze
CNS toxicity
oxidative DNA lesions
nutritive DNA lesions
cytokines
neurodegenerative diseases
spatial learning
spatial memory
Type
thesis
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