ABSTRACT
BACKGROUND@#Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice.@*METHODS@#Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method.@*RESULTS@#The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice.@*CONCLUSIONS@#These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.
Subject(s)
Animals , Female , Male , Mice , Pregnancy , Arsenic/toxicity , Arsenites/toxicity , Behavior, Animal/drug effects , Environmental Pollutants/toxicity , Gene Expression/drug effects , Genetic Markers , Maternal Exposure/adverse effects , Mice, Inbred C3H , Oxidative Stress/genetics , Prefrontal Cortex/drug effects , Prenatal Exposure Delayed Effects/psychology , Reverse Transcriptase Polymerase Chain Reaction , Serotonin/metabolism , Social Behavior , Sodium Compounds/toxicityABSTRACT
Objective@#This study determined the correlation between erythrocyte acetylcholinesterase (AChE) activity, serum malondialdehyde (MDA) and insulin sensitivity in agricultural workers and non-agricultural workers.@*Methodology@#The cross-sectional comparative study was undertaken in 45 agricultural and 45 non-agricultural workers from Nat-Kan Village, Magway Township. Erythrocyte acetylcholinesterase activity and serum malondialdehyde were measured by spectrophotometric method. Insulin sensitivity was calculated by homeostasis model assessment (HOMA-IR).@*Results@#Mean erythrocyte AChE activity was significantly lower in agricultural (3553.99 IU/L) compared with non-agricultural workers (4432.68 IU/L) (p<0.001). A significant high level of mean serum MDA was observed in agricultural workers (0.74 versus 0.28 μmol/L, p<0.001). Median HOMA-IR value was significantly higher in agricultural (2.74) than that of non-agricultural workers (2.28) (p<0.05). The risk of insulin resistance was 2.8 times greater in agricultural workers than non-agricultural workers (OR 2.8, 95% CI, 1.18 to 6.72). Erythrocyte AChE activity had weak negative correlation with serum MDA level (r=-0.357, p<0.001) and HOMA-IR (ρ= -0.305, p<0.05). There was a significant but weak positive correlation between serum MDA level and HOMA-IR (ρ=0.355, p<0.001).@*Conclusion@#Organophosphate pesticide exposure lowered erythrocyte AChE activity and increased oxidative stress. Oxidative stress is partly attributed to the development of insulin resistance